Publications by authors named "Oren Cahlon"

61 Publications

Application of an automatic segmentation method for evaluating cardiac structure doses received by breast radiotherapy patients.

Phys Imaging Radiat Oncol 2021 Jul 23;19:138-144. Epub 2021 Aug 23.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States.

Background And Purpose: Quantifying radiation dose to cardiac substructures is important for research on the etiology and prevention of complications following radiotherapy; however, segmentation of substructures is challenging. In this study we demonstrate the application of our atlas-based automatic segmentation method to breast cancer radiotherapy plans for generating radiation doses in support of late effects research.

Material And Methods: We applied our segmentation method to contour heart substructures on the computed tomography (CT) images of 70 breast cancer patients who received external photon radiotherapy. Two cardiologists provided manual segmentation of the whole heart (WH), left/right atria, left/right ventricles, and left anterior descending artery (LAD). The automatically contours were compared with manual delineations to evaluate similarity in terms of geometry and dose.

Results: The mean Dice similarity coefficient between manual and automatic segmentations was 0.96 for the WH, 0.65 to 0.82 for the atria and ventricles, and 0.06 for the LAD. The mean average surface distance was 1.2 mm for the WH, 3.4 to 4.1 mm for the atria and ventricles, and 6.4 mm for the LAD. We found the dose to the cardiac substructures based on our automatic segmentation agrees with manual segmentation within expected observer variability. For left breast patients, the mean absolute difference in mean dose was 0.1 Gy for the WH, 0.2 to 0.7 Gy for the atria and ventricles, and 1.8 Gy for the LAD. For right breast patients, these values were 0.0 Gy, 0.1 to 0.4 Gy, and 0.4 Gy, respectively.

Conclusion: Our automatic segmentation method will facilitate the development of radiotherapy prescriptive criteria for mitigating cardiovascular complications.
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http://dx.doi.org/10.1016/j.phro.2021.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397890PMC
July 2021

Are 5-Year Randomized Clinical Trial Results Sufficient for Implementation of Short-Course Whole Breast Radiation Therapy?

Pract Radiat Oncol 2021 Sep-Oct;11(5):301-304

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

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http://dx.doi.org/10.1016/j.prro.2021.03.011DOI Listing
November 2020

Development and Pilot Implementation of a Remote Monitoring System for Acute Toxicity Using Electronic Patient-Reported Outcomes for Patients Undergoing Radiation Therapy for Breast Cancer.

Int J Radiat Oncol Biol Phys 2021 Jul 24. Epub 2021 Jul 24.

Departments of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Purpose: We aimed to develop and study the implementation of a remote system for toxicity assessment and management of acute side effects of breast radiation using electronic patient-reported outcomes (ePROs).

Methods And Materials: A response-adapted Patient-Reported Outcomes Common Terminology Criteria for Adverse Events-based assessment for breast radiation toxicity was administered weekly during and for 8 weeks after radiation from June 2019 to July 2020. The care team received alerts when "severe" symptoms were reported by patients, who were then contacted. Treatment, clinic, and sociodemographic characteristics were abstracted from patient records. A subsample of patients and care team members was qualitatively interviewed at follow-up.

Results: Overall, 5787 assessments were sent to 678 patients, of whom 489 (72%) completed 2607 assessments (45%). Moderate or greater toxicity was reported by 419 responders (86%; 95% CI, 82%-89%). Clinician alerts for severe toxicity were generated for 264 assessments among 139 unique patients, of which 83% occurred posttreatment. The proportion of surveys that prompted an alert was significantly higher after treatment (219 [13%]) than during treatment (45 [5%]) (P < .001). Survey completion rates in the posttreatment period were higher among patients undergoing partial breast irradiation than postmastectomy radiation (incidence rate ratio, 0.70; 95% CI, 0.60-0.81) (P < .001) despite these patients experiencing less severe toxicity. Interviews (15) found that patients had a positive experience with ePROs, although many thought the primary purpose was for research rather than symptom management.

Conclusions: With the majority of toxicity occurring after breast radiation has ended, remote symptom monitoring with ePROs appears to fill a gap in clinical practice, particularly for patients undergoing shorter courses of radiation. It is important to properly onboard patients and explain that the purpose of ePROs is to aid clinical care. Further research is needed to determine whether the costs associated with ePROs can be offset by reducing routine clinic visits and whether this approach is acceptable and appropriate.
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http://dx.doi.org/10.1016/j.ijrobp.2021.07.1692DOI Listing
July 2021

Tolerability of Breast Radiotherapy Among Carriers of Germline Variants.

JCO Precis Oncol 2021 19;5. Epub 2021 Jan 19.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

, a gene that controls repair of DNA double-strand breaks, confers an excess lifetime risk of breast cancer among carriers of germline pathogenic variants (PV). PV homozygotes are particularly sensitive to DNA damage caused by ionizing radiation. Consequently, there is concern that adjuvant radiotherapy (RT) may cause excess morbidity among heterozygous carriers of PV. We evaluated the tolerability of breast RT among carriers of germline variants.

Methods: Of 167 patients with germline variants presenting to our institution with breast cancer, 91 received RT. Treatment-related toxicity was ascertained from medical records and graded across organ systems. Toxicities grade > 2 were recorded from the end of treatment to last evaluable follow-up and were analyzed according to variant pathogenicity.

Results: Of 91 evaluable carriers of variants, with a median follow-up of 32 months following RT, 25% (n = 23) harbored a PV, whereas 75% (n = 68) harbored a variant of uncertain significance (VUS). Prevalence of grade ≥ 2 toxicity unrelated to post-mastectomy reconstruction among patients with PV was: 32% at the end of treatment ( 34% for VUS carriers), 11% at 1 year of follow-up ( 4% for VUS carriers), and 8% at the last follow-up ( 13% for VUS carriers), consistent with previous studies of RT among unselected populations. No grade 4 or 5 toxicities were observed. variant pathogenicity was not associated with local toxicity, contralateral breast cancer, or secondary malignancy in this limited cohort of patients who received breast RT.

Conclusion: We found no evidence of excess RT-associated toxicity among carriers of pathogenic germline variants. Breast-conserving therapy and adjuvant RT may be safely considered among appropriately selected carriers of germline variants.
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http://dx.doi.org/10.1200/PO.20.00334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232182PMC
January 2021

Perineural invasion as a risk factor for locoregional recurrence of invasive breast cancer.

Sci Rep 2021 Jun 17;11(1):12781. Epub 2021 Jun 17.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 22, New York, NY, 10044, USA.

Perineural invasion (PNI) is a pathologic finding observed across a spectrum of solid tumors, typically with adverse prognostic implications. Little is known about how the presence of PNI influences locoregional recurrence (LRR) among breast cancers. We evaluated the association between PNI and LRR among an unselected, broadly representative cohort of breast cancer patients, and among a propensity-score matched cohort. We ascertained breast cancer patients seen at our institution from 2008 to 2019 for whom PNI status and salient clinicopathologic features were available. Fine-Gray regression models were constructed to evaluate the association between PNI and LRR, accounting for age, tumor size, nodal involvement, estrogen receptor (ER), progesterone receptor (PR), HER2 status, histologic tumor grade, presence of lymphovascular invasion (LVI), and receipt of chemotherapy and/or radiation. Analyses were then refined by comparing PNI-positive patients to a PNI-negative cohort defined by propensity score matching. Among 8864 invasive breast cancers, 1384 (15.6%) were noted to harbor PNI. At a median follow-up of 6.3 years, 428 locoregional recurrence events were observed yielding a 7-year LRR of 7.1% (95% CI 5.5-9.1) for those with PNI and 4.7% (95% CI 4.2-5.3; p = 0.01) for those without. On univariate analysis throughout the entire cohort, presence of PNI was significantly associated with an increased risk of LRR (HR 1.39, 95% CI 1.08-1.78, p < 0.01). Accounting for differences in salient clinicopathologic and treatment parameters by multivariable Fine-Gray regression modeling, the association between PNI and LRR was potentiated (HR 1.57, 95% CI 1.2-2.07, p = 0.001). We further conducted propensity score matching to balance clinicopathologic parameters and treatments between the two groups (PNI vs not), again showing a similar significant association between PNI and LRR (HR 1.46, 95% CI 1.03-2.08, p = 0.034). PNI is significantly associated with LRR following the definitive treatment of invasive breast cancer. The excess risk conferred by PNI is similar in magnitude to that observed with LVI, or by ER/PR negativity. Breast cancer prognostication and therapeutic decision-making should consider the presence of PNI among other salient risk factors. Larger studies among more uniform breast cancer presentations may elucidate the extent to which these findings apply across breast cancer subtypes and stages.
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http://dx.doi.org/10.1038/s41598-021-92343-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211664PMC
June 2021

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee.

Int J Radiat Oncol Biol Phys 2021 10 25;111(2):337-359. Epub 2021 May 25.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.
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http://dx.doi.org/10.1016/j.ijrobp.2021.05.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416711PMC
October 2021

Proton Therapy for Partial Breast Irradiation: Rationale and Considerations.

J Pers Med 2021 Apr 9;11(4). Epub 2021 Apr 9.

Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, New York, NY 10065, USA.

In an era of continued advancements in personalized medicine for the treatment of breast cancer, select patients with early stage breast cancer may be uniquely poised to benefit from partial breast irradiation (PBI) delivered with proton therapy. PBI presents an opportunity to improve quality of life during treatment with a significantly shorter treatment duration. By targeting less non-target breast tissue, excess radiation exposure and resulting toxicities are also reduced. Proton therapy represents a precision radiotherapy technology that builds on these advantages by further limiting the normal tissue exposure to unnecessary radiation dose not only to uninvolved breast tissue but also the underlying thoracic organs including the heart and lungs. Herein, we present a concise review of the rationale for the use of proton therapy for PBI, evidence available to date, and practical considerations in the implementation and use of proton therapy for this indication.
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http://dx.doi.org/10.3390/jpm11040289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069416PMC
April 2021

Novel Inpatient Radiation Oncology Consult Service Model Reduces Hospital Length of Stay.

JCO Oncol Pract 2021 Mar 31:OP2000923. Epub 2021 Mar 31.

Precision Radiation for Oligometastatic and Metastatic Disease (PROMISE) Program, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Palliative care and radiation therapy have played an expanding role in the management of patients with advanced cancers. Recent advances in our understanding of oligometastatic disease have led to increasing demand for familiarity with ablative techniques. Recognizing the demands of hospitalized patients for rapid access to care, we created an inpatient radiation oncology consult service (IROC) with consolidated expertise in palliative radiation and ablative techniques. In this quality improvement cohort study, we analyzed inpatient radiation oncology consults placed before and after IROC implementation and found that IROC led to increased delivery of specialty care and decreased hospital length of stay (median 8 days 7 days, = .005). This difference was most pronounced for patients for whom radiation therapy was indicated (14.5 11 days, = .007). Our institutional experience demonstrates the value of recognizing metastatic disease as a distinct discipline and providing rapid access to palliative treatments for patients with advanced malignancies.
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http://dx.doi.org/10.1200/OP.20.00923DOI Listing
March 2021

Salvage of locally recurrent breast cancer with repeat breast conservation using 45 Gy hyperfractionated partial breast re-irradiation.

Breast Cancer Res Treat 2021 Jul 26;188(2):409-414. Epub 2021 Mar 26.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 22, New York, NY , 10044, USA.

Purpose: Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase two study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e., 45 Gy administered in 30 fractions of 1.5 Gy twice-daily to the partial breast, "rePBI"). We adopted this regimen as our institutional standard and report our observations regarding the safety and efficacy of rePBI as salvage therapy.

Methods: All patients at our institution who underwent repeat BCT and subsequently received rePBI from 2011 to 2019 were identified. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities.

Results: The cohort included 34 patients with a median age of 65.8 (46.2-78.2) at the time of rePBI. At a median follow-up of 23.5 months, there were two subsequent locoregional recurrences (2-year local control rate 97%). There was no grade ≥ 3 toxicity. The most common acute toxicity (< 3 months) was radiation dermatitis (100%), and common grade 1-2 late toxicities (> 3 months) included fibrosis in 14 (41%), breast asymmetry in 12 (35%), and chest wall pain in 11 (32%).

Conclusions: Repeat breast conservation using the hyperfractionated partial breast RT regimen defined by RTOG 1014 (45 Gy administered in 30 1.5 Gy twice-daily fractions) appears effective and well tolerated. No grade 3 or higher toxicities were observed and local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.
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http://dx.doi.org/10.1007/s10549-021-06206-7DOI Listing
July 2021

Breast conservation among older patients with early-stage breast cancer: Locoregional recurrence following adjuvant radiation or hormonal therapy.

Cancer 2021 Jun 26;127(11):1749-1757. Epub 2021 Jan 26.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both.

Methods: This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis.

Results: There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups.

Conclusions: LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.
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http://dx.doi.org/10.1002/cncr.33422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113065PMC
June 2021

Impact of Telemedicine on Patient Satisfaction and Perceptions of Care Quality in Radiation Oncology.

J Natl Compr Canc Netw 2021 Jan 4:1-7. Epub 2021 Jan 4.

1Department of Radiation Oncology.

Background: The COVID-19 pandemic has transformed cancer care with the rapid expansion of telemedicine, but given the limited use of telemedicine in oncology, concerns have been raised about the quality of care being delivered. We assessed the patient experience with telemedicine in routine radiation oncology practice to determine satisfaction, quality of care, and opportunities for optimization.

Patients And Methods: Patients seen within a multistate comprehensive cancer center for prepandemic office visits and intrapandemic telemedicine visits in December 2019 through June 2020 who completed patient experience questionnaires were evaluated. Patient satisfaction between office and telemedicine consultations were compared, patient visit-type preferences were assessed, and factors associated with an office visit preference were determined.

Results: In total, 1,077 patients were assessed (office visit, n=726; telemedicine, n=351). The telemedicine-consult survey response rate was 40%. No significant differences were seen in satisfaction scores between office and telemedicine consultations, including the appointment experience versus expectation, quality of physician's explanation, and level of physician concern and friendliness. Among telemedicine survey respondents, 45% and 34% preferred telemedicine and office visits, respectively, and 21% had no preference for their visit type. Most respondents found their confidence in their physician (90%), understanding of the treatment plan (88%), and confidence in their treatment (87%) to be better or no different than with an office visit. Patients with better performance status and who were married/partnered were more likely to prefer in-person office visit consultations (odds ratio [OR], 1.04 [95% CI, 1.00-1.08]; P=.047, and 2.41 [95% CI, 1.14-5.47]; P=.009, respectively). Patients with telephone-only encounters were more likely to report better treatment plan understanding with an office visit (OR, 2.25; 95% CI, 1.00-4.77; P=.04).

Conclusions: This study is the first to assess telemedicine in routine radiation oncology practice, and found high patient satisfaction and confidence in their care. Optimization of telemedicine in oncology should be a priority, specifically access to audiovisual capabilities that can improve patient-oncologist communication.
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http://dx.doi.org/10.6004/jnccn.2020.7687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254817PMC
January 2021

10-Year Breast Cancer Outcomes in Women ≤35 Years of Age.

Int J Radiat Oncol Biol Phys 2021 03 24;109(4):1007-1018. Epub 2020 Oct 24.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York. Electronic address:

Purpose: Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.

Methods And Materials: Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology.

Results: A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P <.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P <.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P < .001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P <.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer.

Conclusion: Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006530PMC
March 2021

Replacing 30 Gy in 10 fractions with stereotactic body radiation therapy for bone metastases: A large multi-site single institution experience 2016-2018.

Clin Transl Radiat Oncol 2020 Nov 8;25:75-80. Epub 2020 Oct 8.

Department of Radiation Oncology, Precision Radiation for Oligometastatic and Metastatic Disease (PROMISE) Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Bone metastases cause significant morbidity in patients with cancer, and radiation therapy (RT) is an effective treatment approach. Indications for more complex ablative techniques are emerging. We sought to evaluate RT trends at a large multi-site tertiary cancer center.

Methods: Patients who received RT for bone metastases at a single institution (including regional outpatient clinics) from 2016 to 2018 were identified. Patients were grouped by RT regimen: single-fraction conventional RT (8 Gy × 1), 30 Gy in 10 fractions, SBRT, and "other". Multinomial logistic regression was performed to assess trends in regimens over time. Binary logistic regression was performed to evaluate factors associated with receipt of SBRT.

Results: Between 2016 and 2018, 5,952 RT episodes were received by 2,969 patients with bone metastases. Overall, 76% of episodes were ≤ 5 fractions. The median number of fractions planned for SBRT and non-SBRT episodes was 3 (IQR 3-3) and 5 (IQR 5-10), respectively. Use of SBRT increased from 2016 to 2018 (39% to 53%, p < 0.01) while use of 30 Gy in 10 fractions decreased (26% to 12%, p < 0.01), and 8 Gy × 1 was stable (5.3% to 6.9%, p = 0.28). SBRT was associated with higher performance status (p < 0.01) and non-radiosensitive histology (p < 0.01). Use of SBRT increased in the regional network (19% to 48%, p < 0.01) and at the main center (52% to 59%, p = 0.02), but did not increase within 30 days of death. More patients treated with 8 Gy × 1 than SBRT died within 30 days of treatment (24% vs 3.8%, respectively, p < 0.01).

Conclusions: SBRT is replacing 30 Gy in 10 fractions for bone metastases, especially among patients with high performance status and non-radiosensitive histologies. Better prognostic algorithms could further improve patient-centered treatment selection at the end of life.
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http://dx.doi.org/10.1016/j.ctro.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575833PMC
November 2020

Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer.

JAMA Netw Open 2020 10 1;3(10):e2018790. Epub 2020 Oct 1.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear.

Objective: To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation.

Design, Setting, And Participants: This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020.

Exposures: Untreated metastatic breast cancer.

Main Outcome And Measures: The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings.

Results: Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival.

Conclusions And Relevance: These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.18790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547365PMC
October 2020

Radiation Oncologist Perceptions of Telemedicine from Consultation to Treatment Planning: A Mixed-Methods Study.

Int J Radiat Oncol Biol Phys 2020 Oct;108(2):421-429

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Purpose: Telemedicine was rapidly implemented for initial consultations and radiation treatment planning in the wake of the coronavirus disease 2019 (COVID-19) pandemic. In this study, we explore utilization of and physician perspectives on this approach in an attempt to identify patient populations that may benefit most from virtual care.

Methods And Materials: This is a mixed-methods study with a convergent design. Approximately 6 to 8 weeks after implementation of telemedicine, all radiation oncologists in a single academic radiation oncology department were invited to participate in either semistructured interviews with embedded survey questions or a concurrently administered survey only. Rapid qualitative analysis was used to identify common themes, and quantitative data was assessed using descriptive statistics and univariable analyses.

Results: At the apex of the pandemic, 92% of radiation oncology visits were conducted via telemedicine. In total, 51 of 61 radiation oncologists participated in the study (response rate 84%). Most (71%) reported no difference in ability to treat cancer appropriately via telemedicine, which was more common among specialized physicians (P = .01) but not those with higher visit volume or years of experience. Over half (55%) perceived no difference or even improvement in overall visit quality with telemedicine. Virtual visits were deemed acceptable for a median of 70% to 96% of patients, which varied by disease site. Need for physical examination, and availability of an acceptable proxy, factored into telemedicine acceptability. Most (88%) found telemedicine better than expected, but opinions were split on how telemedicine would affect physician burnout. Almost all (96%) foresaw a role for telemedicine beyond the pandemic and would opt for a median of 50% (interquartile range 20%-66%) of visits conducted via telemedicine.

Conclusions: Among radiation oncologists in an academic setting, telemedicine was perceived to be highly appropriate and acceptable for most patients. Future studies should focus on identifying the 5% to 30% of patients whose care may be optimized with in-person visits, and if there is alignment with patient preferences.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462757PMC
October 2020

A dosimetry study of post-mastectomy radiation therapy with AeroForm tissue expander.

J Appl Clin Med Phys 2020 Sep 2;21(9):33-38. Epub 2020 Jul 2.

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: To evaluate the dosimetric effects of the AeroForm (AirXanpders®, Palo Alto, CA) tissue expander in-situ for breast cancer patients receiving post-mastectomy radiation therapy.

Methods And Materials: A film phantom (P1) was constructed by placing the metallic canister of the AeroForm on a solid water phantom with EBT3 films at five depths ranging from 2.6 mm to 66.2 mm. A breast phantom (P2), a three-dimensional printed tissue-equivalent breast with fully expanded AeroForm in-situ, was placed on a thorax phantom. A total of 21 optical luminescent dosimeters (OLSDs) were placed on the anterior skin-gas interface and the posterior chest wall-metal interface of the AeroForm. Both phantoms were imaged with a 16-bit computed tomography scanner with orthopedic metal artifact reduction. P1 was irradiated with an open field utilizing 6 MV and 15 MV photon beams at 0°, 90°, and 270°. P2 was irradiated using a volumetric modulated arc therapy plan with a 6 MV photon beam and a tangential plan with a 15 MV photon beam. All doses were calculated using Eclipse (Varian, Palo Alto, CA) with AAA and AcurosXB (AXB) algorithms.

Results: The average dose differences between film measurements and AXB in the region adjacent to the canister in P1 were within 3.1% for 15 MV and 0.9% for 6 MV. Local dose differences over 10% were also observed. In the chest wall region of P2, the median dose of OLSDs in percentage of prescription dose were 108.4% (range 95.4%-113.0%) for the 15MV tangential plan and 110.4% (range 99.1%-113.8%) for the 6MV volumetric modulated arc therapy plan. In the skin-gas interface, the median dose of the OLSDs were 102.3% (range 92.7%-107.7%) for the 15 MV plan and 108.2% (range 97.8-113.5%) for the 6 MV plan. Measured doses were, in general, higher than calculated doses with AXB calculations. The AAA dose algorithms produced results with slightly larger discrepancies between measurements compared with AXB.

Conclusions: The AeroForm creates significant dose uncertainties in the chest wall-metal interface. The AcurosXB dose calculation algorithm is recommended for more accurate calculations. If possible, post-mastectomy radiation therapy should be delivered after the permanent implant is in place.
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http://dx.doi.org/10.1002/acm2.12962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497932PMC
September 2020

Breast Radiation Therapy Under COVID-19 Pandemic Resource Constraints-Approaches to Defer or Shorten Treatment From a Comprehensive Cancer Center in the United States.

Adv Radiat Oncol 2020 Jul-Aug;5(4):582-588. Epub 2020 Apr 1.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Breast radiation therapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice. In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered. Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiation therapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization.

Methods And Materials: Multidisciplinary breast cancer experts at a high-volume comprehensive cancer center convened contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the application of hypofractionated and abbreviated breast radiation regimens.

Results: Substantial evidence exists to support omitting radiation among certain favorable risk subgroups of patients with breast cancer and for abbreviating or accelerating regimens among others. For those who require either whole-breast or postmastectomy radiation, with or without coverage of the regional lymph nodes, a growing body of literature supports various hypofractionated approaches that appear safe and effective.

Conclusions: In the setting of a public health emergency with the potential to strain critical healthcare resources and place patients at risk of infection, the parsimonious application of breast radiation therapy may alleviate a significant clinical burden without compromising long-term oncologic outcomes. The judicious and personalized use of immature study data may be warranted in the setting of a competing mortality risk from this widespread pandemic.
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http://dx.doi.org/10.1016/j.adro.2020.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118660PMC
April 2020

Patterns of Recurrence Among Higher-Risk Patients Receiving Daily External Beam Accelerated Partial-Breast Irradiation to 40 Gy in 10 Fractions.

Adv Radiat Oncol 2020 Jan-Feb;5(1):27-33. Epub 2019 Aug 6.

Department of Radiation Oncology.

Purpose: The 2016 American Society for Radiation Oncology consensus guidelines for the use of accelerated partial-breast irradiation (APBI) define "suitable," "cautionary," and "unsuitable" populations for this adjuvant breast radiation therapy technique. We sought to determine whether patients in the cautionary group exhibited adverse outcomes after APBI compared with their suitable counterparts.

Methods And Materials: We identified 252 consecutively treated patients from a single institution with in situ or early-stage invasive breast cancer who underwent APBI between 2008 and 2017. Treatment technique was uniform throughout the population, consisting of 3-dimensional conformal radiation therapy to 40 Gy administered in 10 daily fractions.

Results: One hundred seventy-eight patients (70%) were classified as suitable, 69 (27%) as cautionary, and 5 (2.0%) as unsuitable. Because unsuitable patients were few and had no recurrences, they were excluded from analysis. At a median follow-up time of 3.9 years, 97.2% of patients were free of recurrence. Four patients (1.5% overall; 3 suitable and 1 cautionary) experienced ipsilateral in-breast recurrences, and 1 cautionary patient developed an ipsilateral regional recurrence in an axillary lymph node. There was no significant difference in the rate of ipsilateral breast recurrence (2.4% vs 1.0%) between cautionary and suitable groups.

Conclusions: Local recurrences are rare among guideline-defined cautionary patients with in situ or invasive breast cancer treated with APBI delivered via daily 3-dimensional conformal radiation therapy to 40 Gy. At a median follow-up of 3.9 years, no significant differences in local control were noted between cautionary and suitable patient groups. Further study is needed to characterize long-term disease outcomes among various risk groups.
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http://dx.doi.org/10.1016/j.adro.2019.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004933PMC
August 2019

From Orientation to Onboarding: A Survey-Based Departmental Improvement Program for New Radiation Oncology Faculty Physicians.

JCO Oncol Pract 2020 04 6;16(4):e395-e404. Epub 2020 Feb 6.

Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: To evaluate physician-reported assessments of an established faculty orientation program for new radiation oncology physicians at a large academic center and to prospectively analyze the effects of an onboarding improvement program based on those assessments.

Materials And Methods: An anonymous survey was designed and distributed to physicians new to the department who received onboarding orientation between 2013 and 2017. Survey questions addressed the comprehensiveness, effectiveness, and utility of various orientation activities. On the basis of the survey results, an improved onboarding program was designed and implemented for nine new faculty members between May 2018 and November 2018. A post-intervention survey querying topics similar to those in the pre-intervention survey was distributed to the new faculty members. Descriptive statistics were generated to compare the pre-intervention and post-intervention groups.

Results: The overall rate of survey completion was 85% (17 of 20). The intervention program markedly improved physician assessment of comprehensiveness and effectiveness of the onboarding process. Physicians strongly and consistently identified mentor shadowing, on-the-job training, and other faculty mentorship activities as the most important components of an effective onboarding experience.

Conclusion: An enhanced, tailored, person-oriented, formal onboarding improvement program significantly increased physician assessment scores of comprehensiveness and effectiveness of the faculty onboarding process. This model can serve as a framework for increasing physician preparedness, encouraging early physician mentorship, and ensuring a universal standard of quality across large practices.
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http://dx.doi.org/10.1200/JOP.19.00641DOI Listing
April 2020

Feasibility of Breast-Conservation Therapy and Hypofractionated Radiation in the Setting of Prior Breast Augmentation.

Pract Radiat Oncol 2020 Sep - Oct;10(5):e357-e362. Epub 2020 Mar 20.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Cosmetic outcomes and rate of implant loss are poorly characterized among patients with breast cancer with previous breast augmentation (BA) who undergo breast-conservation therapy (BCT). Here we determine capsular contracture and implant loss frequency after BCT among patients receiving contemporary whole-breast radiation therapy (RT).

Methods And Materials: Patients with breast cancer with a history of BA presenting to our institution from January 2006 to January 2017 who elected for BCT were included. Seventy-one breast cancers in 70 patients with a history of BA electing for BCT were retrospectively identified. Clinicopathologic, treatment, and outcome variables were examined. Whole-breast RT included conventional and hypofractionated schedules with and without a boost. Rates of implant loss and cosmetic outcomes among patients who did and did not develop a new/worse contracture based on physician assessment were compared.

Results: In the study, 54.9% of patients received radiation using hypofractionated whole-breast tangents; 81.7% received a boost. In addition, 18 out of 71 cases (25.4%) developed a new/worse contracture after BCT with a mean follow-up of 1.9 years. Furthermore, 9 out of 71 cases (12.7%) were referred to a plastic surgeon for revisional surgery. There were no implant-loss cases. On univariate analysis, implant location, time from implant placement to diagnosis, RT type, RT boost, body mass index, and tumor size were not associated with new/worse contracture. Of 12 patients with existing contracture, only 2 developed worsening contracture. Physician assessment of cosmetic outcome after BCT was noted to be excellent or good for 87.4% of patients.

Conclusions: BCT for breast cancer patients with prior history of BA has a low risk of implant loss. Hypofractionated RT does not adversely affect implant outcomes. Patients should be counseled regarding risk for capsular contracture, but the majority have good/excellent outcome; BA does not represent a contraindication to BCT.
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http://dx.doi.org/10.1016/j.prro.2020.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483319PMC
August 2021

Clinical Outcomes of Recurrent Intracranial Meningiomas Treated with Proton Beam Reirradiation.

Int J Part Ther 2019 1;5(4):11-22. Epub 2019 May 1.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: Recurrent meningiomas remain therapeutically challenging, often progressive despite multimodality salvage. There are limited data guiding reirradiation (reRT), and proton beam radiation therapy (PBRT) offers a potential advantage owing to lower integral brain dose.

Patients And Methods: We retrospectively conducted a review of 16 patients who received PBRT reRT for recurrent meningiomas. Kaplan-Meier and proportional hazards were used to determine post-PBRT progression-free survival (PFS) and overall survival (OS) and to evaluate clinical predictors.

Results: At diagnosis, 7 (44%), 8 (50%), and 1 (6%) patient had World Health Organization (WHO) grade I, II and III tumors, respectively. All received prior radiation therapy (RT) to a median of 54 Gy (range 13-65.5). Median time to PBRT reRT after prior RT was 5.8 years (range 0.7-18.7). Median PBRT dose was 60 Gy(RBE) (range 30-66.6), and median planning tumor volume (PTV) was 76 cm (range 8-249). Median follow-up was 18.8 months. At last follow-up, 7 intracranial recurrences (44%) and 3 disease-related deaths (19%) were found. Median cohort PFS was 22.6 months, with 1- and 2-year PFS of 80% and 43%, respectively. Median OS was not achieved, with 1- and 2-year OS of 94% and 73%; all deaths were felt to be related to meningioma. Patients with initially grade I tumors had improved PFS versus higher grade (Hazard Ratio, HR = 0.23,  = .03) with 1- and 2-year PFS estimates of 100% versus 71% and 75% versus 29%, respectively. Longer interval between prior RT and PBRT also predicted improved PFS ( = .03) and OS ( = .049). Overall late grade 3+ toxicity rate was 31%. Two patients (13%) developed radionecrosis at 6 and 16 months after PBRT; only 1 was symptomatic.

Conclusions: This is the first series specifically analyzing PBRT alone as a reRT strategy for recurrent meningioma. We report fair intracranial control with low rates of radionecrosis at 1 year after reRT. However, strategies to achieve durable outcomes are needed, particularly for high-grade tumors.
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http://dx.doi.org/10.14338/IJPT-18-00045.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871625PMC
May 2019

Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol.

BMJ Open 2019 10 15;9(10):e025556. Epub 2019 Oct 15.

Provision Proton Therapy Center, Knoxville, Tennessee, USA.

Introduction: A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer.

Methods: We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events.

Ethics And Dissemination: The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.

Trial Registration Number: NCT02603341.
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http://dx.doi.org/10.1136/bmjopen-2018-025556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797426PMC
October 2019

Radiotherapy in the setting of hypersensitivity syndromes.

Breast J 2020 03 12;26(3):588-589. Epub 2019 Sep 12.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

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http://dx.doi.org/10.1111/tbj.13621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604742PMC
March 2020

Prevention, Diagnosis, and Management of Radiation-Associated Cardiac Disease: JACC Scientific Expert Panel.

J Am Coll Cardiol 2019 08;74(7):905-927

Department of Cardiothoracic Surgery, Center for Radiation Heart Disease, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.

Radiation-associated cardiac disease, a heterogeneous and complex disease, manifests years or even decades following radiation exposure to the chest. It is associated with a significantly higher morbidity and mortality. Often, the presentation is vague and overlaps with many diseases, presenting unique diagnostic and management issues. As a result, a high index of suspicion followed by multimodality imaging is crucial, along with comprehensive screening to enable early detection. Timing of intervention should be carefully considered in these patients, because surgery is often complex with an emerging role of percutaneous interventions.
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http://dx.doi.org/10.1016/j.jacc.2019.07.006DOI Listing
August 2019

Overall Survival of Breast Cancer Patients With Locoregional Failures Involving Internal Mammary Nodes.

Adv Radiat Oncol 2019 Jul-Sep;4(3):447-452. Epub 2019 Mar 1.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Internal mammary node recurrence after definitive breast cancer treatment is poorly characterized, with limited data to guide clinical management. The aim of this study was to analyze the outcomes of patients with recurrent breast cancer involving internal mammary nodes to understand their natural history and determine prognostic factors associated with improved overall survival.

Methods And Materials: We performed a retrospective analysis of 553 patients with recurrent breast cancer and identified 161 patients with radiographic evidence of locoregional recurrence as a first event. A total of 67 patients (42%) were identified with internal mammary involvement. Median follow-up times were 76 months from date of initial diagnosis and 30 months from date of recurrence.

Results: Of the 67 patients identified with internal mammary node failures, 10 (15%) presented with isolated recurrence, 14 (21%) presented with other sites of locoregional disease, and 43 (64%) presented with concomitant distant metastases. Median overall survival was 2.5 years and significantly associated with extent of disease ( < .0001). On multivariable analysis, concomitant distant metastases, inflammatory breast cancer, and triple negative histologic type were associated with worse overall survival, whereas salvage radiation therapy was associated with improved overall survival. Among the 10 patients with isolated internal mammary node failures, median progression-free survival was 6.0 years and salvage therapy with surgery, radiation, and chemotherapy were associated with the best outcomes.

Conclusions: Patients with isolated internal mammary node recurrences achieved long-term survival with aggressive therapies, and salvage radiation therapy was associated with improved survival.
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http://dx.doi.org/10.1016/j.adro.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639740PMC
March 2019

Daily Fractionation of External Beam Accelerated Partial Breast Irradiation to 40 Gy Is Well Tolerated and Locally Effective.

Int J Radiat Oncol Biol Phys 2019 07 7;104(4):859-866. Epub 2019 Mar 7.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Purpose: Most studies examining accelerated partial breast irradiation (APBI) have used twice-daily fractionation. Cosmesis with this approach has produced mixed results, and the optimal fractionation scheme remains unknown. We sought to evaluate the safety and efficacy of APBI with a total dose of 40 Gy in 10 daily fractions.

Methods And Materials: Between 2010 and 2014, we prospectively enrolled 106 patients to receive APBI after lumpectomy for invasive or in situ node-negative breast cancer. Radiation was administered via 3-dimensional conformal techniques.

Results: The median age was 62 years (range, 39-85), and all patients underwent APBI per protocol. With a median follow-up of 58 months, we evaluated patient-reported local toxicity and recurrence outcomes. Of 106 patients, 16 (15%) experienced grade ≥2 skin toxicity. The most common significant toxicities were acute cutaneous changes at 4 to 9 weeks after radiation therapy, including grade 2 erythema in 2 patients (1.8%) and skin color changes in 4 patients (3.8%). Only 2 instances of grade 3 toxicity were reported, including 1 patient with acute moist desquamation after radiation therapy and another with fibrosis at 2 years. Planning target volume and breast V were significantly predictive of skin/subcutaneous toxicity, with evidence that limiting breast V to <45% may improve tolerability. Overall, 3 breast cancer recurrences arose: 1 local recurrence in the original quadrant (3 years after APBI), 1 in a different ipsilateral quadrant (5 years after APBI), and 1 with distant disease 2 years after APBI.

Conclusions: In an appropriately selected group of patients with early stage breast cancer, APBI to a dose of 40 Gy in 10 daily fractions was well tolerated, with most patients (99%) reporting excellent/good cosmesis. Planning target volume and breast V should be carefully constrained to limit local morbidity. Longer follow-up will be needed to establish efficacy and subsequent local recurrence rates.
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http://dx.doi.org/10.1016/j.ijrobp.2019.02.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595753PMC
July 2019

Assessment of Early Radiation-Induced Changes in Left Ventricular Function by Myocardial Strain Imaging After Breast Radiation Therapy.

J Am Soc Echocardiogr 2019 04 28;32(4):521-528. Epub 2019 Feb 28.

Cardiology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.

Background: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT.

Methods: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models.

Results: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT.

Conclusions: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.
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http://dx.doi.org/10.1016/j.echo.2018.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487646PMC
April 2019

Early outcomes of breast cancer patients treated with post-mastectomy uniform scanning proton therapy.

Radiother Oncol 2019 03 7;132:250-256. Epub 2018 Nov 7.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States. Electronic address:

Background: Postmastectomy proton radiotherapy improves normal tissue sparing in comparison to photon-based approaches. Several studies have reported dosimetry comparison and tolerable acute toxicity profile with limited follow-up. We report our institutional experience of postmastectomy proton radiation including clinical efficacy and toxicities.

Methods: From December 2013 to February 2015, 42 consecutive patients who received mastectomy for non-metastatic breast cancer were treated with adjuvant chest wall and regional nodal proton therapy at a single proton center. 3D conformal uniform scanning with en face matching fields was used.

Results: The median follow-up among patients was 35 months (range 1-55 months). There was one local failure, zero regional nodal failure, and six distant failures. The 3-year rate of locoregional disease-free survival was 96.3%, metastasis-free survival was 84.1%, and overall survival was 97.2%. The only local failure event occurred on the chest wall within the radiation field, approximately 2.5 years after the completion of radiation. Skin dermatitis, fatigue, and esophagitis were the most common acute toxicity. All patients developed grade 1 or 2 acute skin toxicity and there was no grade 3 or 4 acute skin toxicity. Proton radiation is able to achieve excellent target coverage with median PTV V95 over 95% and heart sparing with median mean heart dose less than 1 Gy (RBE).

Conclusion: With close to three years of median follow-up, post-mastectomy proton radiation has shown excellent locoregional control rates and favorable toxicity profile. Long-term adverse effect of heart-sparing radiation will require longer follow-up time and randomized clinical trials.
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http://dx.doi.org/10.1016/j.radonc.2018.10.002DOI Listing
March 2019

A 3-Dimensional Mapping Analysis of Regional Nodal Recurrences in Breast Cancer.

Int J Radiat Oncol Biol Phys 2019 03 24;103(3):583-591. Epub 2018 Oct 24.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: The primary goal was to map the anatomic pattern of isolated nodal recurrences (NR) in the supraclavicular (SCV), axillary, and internal mammary nodes (IMNs) in patients with breast cancer treated with curative-intent surgery with or without radiation therapy (RT). Secondary objectives were to assess clinical and pathologic factors associated with patterns of NR and survival rates.

Methods And Materials: Patients with NR after treatment at a single cancer center during 1998 to 2013 were identified. Patients with prior distant metastases or NR without correlative imaging were excluded. All NRs were overlaid onto representative axial computed tomographic images. Multivariable analysis was performed to identify clinical and pathologic characteristics associated with NR. Kaplan-Meier curves were generated to assess the rate of relapse by nodal region according to pathologic feature or radiation treatment status.

Results: The locations of 243 NRs among 153 eligible patients were mapped. The majority of NR occurred in the axilla (42%; 102/243), followed by the IMN (32.5%; 79/243) and the SCV (25.5%; 62/243). Radiation Therapy Oncology Group (RTOG) or European Society for Radiation therapy and Oncology (ESTRO) clinical target volume encompassed 82% (198/243) of NRs. The majority of out-of-field NRs were located in the lateral and posterior SCV region for both RTOG (67%; 30/45) and ESTRO (89%; 49/55) guidelines. The high-risk patients who received regional RT to the SCV relapsed at a similar rate in the medial, but a higher rate in lateral SCV (P = .009), compared with low-risk patients who received no nodal RT. Lymphovascular invasion most strongly associated with IMN NR (P = .001); grade 3 disease highly associated with both IMN (P = .001) and SCV NR (P = .02). The presence of an IMN NR portended for significantly inferior overall survival (OS), compared with an axillary NR, with a 5-year OS of 59% versus 72%, respectively (P = .03).

Conclusions: In this 3-dimensional image-based analysis of NR patterns in breast cancer patients treated with contemporary therapies, the lateral and posterior SCV represented a distinct site of NR that is not routinely included within current breast cancer contouring atlases. Grade 3 breast cancer and LVI were most commonly associated with the development of NR in the SCV. Modifying the CTV to encompass the lateral and posterior SCV in patients with breast cancer with these features might be justified.
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http://dx.doi.org/10.1016/j.ijrobp.2018.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135107PMC
March 2019

Proton Radiotherapy for Recurrent or Metastatic Head and Neck Cancers with Palliative Quad Shot.

Int J Part Ther 2018 ;4(4):10-19

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: Some patients with previously treated, unresectable, recurrent or metastatic head and neck malignancies are not amenable to curative-intent treatment. Here, we investigated the quad-shot (RTOG 8502) regimen of hypofractionated proton radiotherapy (RT) in that patient population.

Materials And Methods: From 2013 to 2015, 26 patients with recurrent or metastatic cancers were treated with palliative proton RT to the head and neck with quad shot (3.7 Gy twice daily for 2 days). Patient characteristics and survival data were reviewed.

Results: Seventeen (65%) patients received ≥ 3 quad-shot cycles and 23 (88%) had prior head and neck RT. Overall palliative response was 73% (n = 19). The most common presenting symptom was pain (50%; n = 13), which improved in 85% (n = 22) of all patients. The overall grade-1 acute-toxicity rate was 58% (n = 15), and no acute grade 3 to 5 toxicities were observed.

Conclusions: The proton quad-shot regimen demonstrates favorable palliative response and toxicity profile, even in patients that received prior RT.
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http://dx.doi.org/10.14338/IJPT-18-00003.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145811PMC
January 2018
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