Publications by authors named "Atif J Khan"

89 Publications

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

Cost-Effectiveness Analysis of No Adjuvant Therapy Versus Partial Breast Irradiation Alone Versus Combined Treatment for Treatment of Low-Risk DCIS: A Microsimulation.

JCO Oncol Pract 2021 Aug 10;17(8):e1055-e1074. Epub 2021 May 10.

Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.

Purpose: Adjuvant therapy in patients with ductal carcinoma in situ who undergo partial mastectomy remains controversial, particularly for low-risk patients (60 years or older, estrogen-positive, tumor extent < 2.5 cm, grade 1 or 2, and margins ≥ 3 mm). We performed a cost-effectiveness analysis comparing three strategies: no adjuvant treatment after surgery, a five-fraction course of accelerated partial breast irradiation using intensity-modulated radiation therapy (accelerated partial breast irradiation [APBI]-alone), or APBI plus an aromatase inhibitor for 5 years.

Materials And Methods: Outcomes including local recurrence, distant metastases, and survival as well as toxicity data were modeled by a patient-level Markov microsimulation model, which were validated against trial data. Costs of treatment and possible adverse events were included from the societal perspective over a lifetime horizon, adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALYs) were calculated based on utilities extracted from the literature.

Results: No adjuvant therapy was the least costly approach ($5,744), followed by APBI-alone ($11,070); combined therapy was costliest ($16,052). Adjuvant therapy resulted in slightly higher QALYs (no adjuvant, 11.320; APBI-alone, 11.343; and combination, 11.381). In the base case, no treatment was the cost-effective strategy, with an incremental cost-effectiveness ratio of $239,109/QALY for APBI-alone and $171,718/QALY for combined therapy. The incremental cost-effectiveness ratio for combined therapy compared with APBI-alone was $131,949. Probabilistic sensitivity analyses found that no therapy was cost effective (defined as $100,000/QALY of lower) in 63% of trials, APBI-alone in 19%, and the combination in 18%.

Conclusion: No adjuvant therapy represents the most cost-effective approach for postmenopausal women 60 years or older who receive partial mastectomy for low-risk ductal carcinoma in situ.
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http://dx.doi.org/10.1200/OP.20.00992DOI Listing
August 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

Outcomes with Partial Breast Irradiation vs. Whole Breast Irradiation: a Meta-Analysis.

Ann Surg Oncol 2021 Sep 3;28(9):4985-4994. Epub 2021 Jan 3.

21st Century Oncology, Michigan Healthcare Professionals, Farmington Hills, MI, USA.

Background: Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques.

Methods: A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI.

Results: A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68-3.2%) and WBI (1.7%, 95% HPD 0.92-2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI.

Conclusions: IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.
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http://dx.doi.org/10.1245/s10434-020-09447-wDOI Listing
September 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

In Reply to Dyer et al.

Int J Radiat Oncol Biol Phys 2021 01;109(1):301-302

Memorial Sloan Kettering Cancer Center, New York, New York.

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http://dx.doi.org/10.1016/j.ijrobp.2020.09.013DOI Listing
January 2021

Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.

J Natl Cancer Inst 2021 03;113(3):266-273

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

Background: Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure.

Methods: We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided.

Results: Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors.

Conclusions: We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.
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http://dx.doi.org/10.1093/jnci/djaa095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936050PMC
March 2021

Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.

Breast Cancer Res Treat 2020 Jul 28;182(2):355-365. Epub 2020 May 28.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

Purpose: We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination.

Methods: We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature.

Results: The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years.

Conclusions: Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.
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http://dx.doi.org/10.1007/s10549-020-05706-2DOI Listing
July 2020

Locoregional Management After Neoadjuvant Chemotherapy.

J Clin Oncol 2020 07 22;38(20):2281-2289. Epub 2020 May 22.

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

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http://dx.doi.org/10.1200/JCO.19.02576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343435PMC
July 2020

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Int J Radiat Oncol Biol Phys 2020 09 14;108(1):227-241. Epub 2020 May 14.

Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.
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http://dx.doi.org/10.1016/j.ijrobp.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646202PMC
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

5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial.

Int J Radiat Oncol Biol Phys 2020 07 11;107(4):694-700. Epub 2020 Apr 11.

Memorial Sloan Kettering Cancer Center, New York City, New York.

Purpose: Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen.

Methods And Materials: Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications.

Results: After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%.

Conclusions: This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373304PMC
July 2020

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

Axillary management for young women with breast cancer varies between patients electing breast-conservation therapy or mastectomy.

Breast Cancer Res Treat 2020 Feb 14;180(1):197-205. Epub 2020 Jan 14.

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA.

Purpose: Axillary treatment strategies for the young woman with early-stage, clinically node-negative breast cancer undergoing upfront surgery found to have 1-3 positive sentinel lymph nodes (SLNs) differ significantly after BCT and mastectomy. Here we compare axillary lymph node dissection (ALND) and regional nodal irradiation (NRI) rates between women electing breast-conservation therapy (BCT) versus mastectomy.

Methods: From 2010 to 2016, women age < 50 years with clinical T1-T2N0 breast cancer having upfront surgery and found to have a positive SLN were identified. ALND and/or NRI receipt were compared between groups.

Results: 192 women undergoing BCT and 165 undergoing mastectomy were identified (median age: 44 years). 5.2% (10/192) of women undergoing BCT had an ALND versus 87% (144/165) of women undergoing mastectomy (p < 0.01). NRI was given to 48% (78/165) of mastectomy patients compared to 30% (57/192) of BCT patients (p < 0.01). Of the 75 mastectomy patients with 1-2 total positive lymph nodes after completion ALND, 44% received NRI. Women undergoing mastectomy were significantly more likely to receive both ALND and NRI than women undergoing BCS (45% vs 6%, p < 0.01).

Conclusion: Young cT1-2N0 breast cancer patients found to have 1-3 SLN metastases received ALND, NRI, and combined ALND/NRI more frequently if they elected mastectomy over BCT. Use of both ALND and postmastectomy radiotherapy (PMRT) in this population could be reduced in the future by omitting ALND in patients for whom the need for PMRT is clear with the finding of 1-2 SLN metastases.
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http://dx.doi.org/10.1007/s10549-019-05520-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035176PMC
February 2020

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

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

5-Year Results of a Prospective Phase 2 Trial Evaluating 3-Week Hypofractionated Whole Breast Radiation Therapy Inclusive of a Sequential Boost.

Int J Radiat Oncol Biol Phys 2019 10 5;105(2):267-274. Epub 2019 Jun 5.

Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Electronic address:

Purpose: To report 5-year outcomes of a phase 2 trial of hypofractionated whole breast irradiation (HF-WBI) completed in 3 weeks, inclusive of a sequential boost.

Methods And Materials: Women with stage 0-IIIA breast cancer (ductal carcinoma in situ through T2N2a) were enrolled on a prospective, phase 2 trial of accelerated HF-WBI. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy, with an equivalent dose to the regional nodes when indicated, followed by a tumor bed boost of 13.32 Gy in 4 fractions of 3.33 Gy over a total of 15 treatment days. The primary endpoint was locoregional control; secondary endpoints included acute/late toxicity and physician-assessed and patient-reported breast cosmesis.

Results: Between 2009 and 2017, we enrolled 150 patients, of whom 146 received the protocol treatment. Median age was 54 years (range, 33-82) and median follow-up was 62 months. Patients with higher-risk disease comprised 59% of the cohort, including features such as young age (33% ≤50 years), positive nodes (13%), triple-negative disease (11%), and treatment with regional nodal irradiation (11%) and/or neoadjuvant/adjuvant chemotherapy (36%). Five-year estimated locoregional and distant control were 97.7% (95% confidence interval [CI], 93.0%-99.3%) and 97.9% (95% CI, 93.6%-99.3%), respectively. Five-year breast cancer-specific and overall survival were 99.2% (95% CI, 94.6%-99.9%) and 97.3% (95% CI, 91.9%-99.1%), respectively. Acute/late grade 2 and 3 toxicities were observed in 30%/10% and 1%/3% of patients, respectively. There were no grade 4 or 5 toxicities. Physicians assessed breast cosmesis as good or excellent in 95% of patients; 85% of patients self-reported slight to no difference between the treated and untreated breast.

Conclusions: Our phase 2 trial offers one of the shortest courses of HF-WBI; at 5 years of follow-up there continues to be excellent locoregional control and low toxicity with favorable cosmetic outcomes in a heterogeneous cohort of patients.
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http://dx.doi.org/10.1016/j.ijrobp.2019.05.063DOI Listing
October 2019

In Reply to Yadav and Gupta, and Hannoun-Levi et al.

Authors:
Atif J Khan

Int J Radiat Oncol Biol Phys 2019 07;104(3):700

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

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http://dx.doi.org/10.1016/j.ijrobp.2019.03.023DOI Listing
July 2019

The glutamate release inhibitor riluzole increases DNA damage and enhances cytotoxicity in human glioma cells, and .

Oncotarget 2019 Apr 19;10(29):2824-2834. Epub 2019 Apr 19.

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.

Purpose: High-grade gliomas are lethal malignancies that cause morbidity and mortality due to local progression rather than metastatic spread. Our group has previously demonstrated that human GRM1 (hGRM1) is ectopically expressed in melanocytes leading to a transformed phenotype. Riluzole, a glutamate release inhibitor, leads to apoptotic cell death via DNA damage. Recent work has demonstrated the pathological significance of the related mGluR3/GRM3 (protein or gene: hGRM3) in gliomas. We evaluated the effect of riluzole on glioma cells.

Experimental Design: Western blot analysis and immunofluorescence was performed to assess for GRM3 expression in commercially available and patient-derived glioma cells and for functional analysis of GRM3 using receptor agonist/antagonists and downstream effectors, ERK and AKT phosphorylation, as the read-out. Glutamate secretion by glioma cells was measured using ELISA. Flank and intracranial mouse xenograft models were used to assess growth delay with the glutamate release inhibitor, riluzole (RIL). Immunofluorescence was used to evaluate 53BP1 or γ-H2AX foci after RIL.

Results: GRM3 was expressed in most tested glioma samples, and strongly expressed in some. Glioma cells were found to secrete glutamate in the extracellular space and to respond to receptor stimulation by activating downstream ERK. This signaling was abrogated by pretreatment with RIL. Treatment with RIL caused an increase in DNA damage markers, and an increase in cellular cytotoxicity and .

Conclusions: We have demonstrated that pretreatment with the glutamate-release inhibitor riluzole sensitizes glioma cells to radiation and leads to greater cytotoxicity; these results have clinical implications for patients with glioblastoma.
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http://dx.doi.org/10.18632/oncotarget.26854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497458PMC
April 2019

A Current Review of Spatial Fractionation: Back to the Future?

Int J Radiat Oncol Biol Phys 2019 05 23;104(1):177-187. Epub 2019 Jan 23.

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

Spatially fractionated radiation therapy represents a significant departure from canonical thinking in radiation oncology despite having origins in the early 1900s. The original and most common implementation of spatially fractionated radiation therapy uses commercially available blocks or multileaf collimators to deliver a nonconfluent, sieve-like pattern of radiation to the target volume in a nonuniform dose distribution. Dosimetrically, this is parameterized by the ratio of the valley dose in cold spots to the peak dose in hot spots, or the valley-to-peak dose ratio. The radiobiologic mechanisms are postulated to involve radiation-induced bystander effects, microvascular alterations, and/or immunomodulation. Current indications include bulky or locally advanced disease that would not be amenable to conventional radiation or that has proved refractory to chemoradiation. Early-phase clinical trials have shown remarkable success, with some response rates >90% and minimal toxicity. This has promoted technological developments in 3-dimensional formats (LATTICE), micron-size beams (microbeam), and proton arrays. Nevertheless, more clinical and biological data are needed to specify ideal dosimetry parameters and to formulate robust clinical indications and guidelines for optimal standardized care.
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http://dx.doi.org/10.1016/j.ijrobp.2019.01.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443362PMC
May 2019

Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Brachytherapy Applicators Is Feasible and Safe: First Results From the TRIUMPH-T Trial.

Int J Radiat Oncol Biol Phys 2019 05 4;104(1):67-74. Epub 2019 Jan 4.

Arizona Breast Cancer Specialists, Scottsdale, Arizona.

Purpose: Shorter courses of accelerated partial-breast irradiation delivered as single-fraction intraoperative therapy are now offered as an alternative to 4 to 6 weeks of whole-breast irradiation after lumpectomy. However, this approach has potential shortcomings in patient selection and target volume definition and in dosimetric, radiobiological, and logistical issues. We designed a prospective, phase 2, multi-institution clinical trial to study 2- or 3-day accelerated partial breast irradiation delivered with brachytherapy applicators.

Methods And Materials: This trial treats select breast cancers after breast-conserving surgery with brachytherapy applicators that deliver 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 1.5 cm beyond the surgical cavity. Eligible women were aged ≥45 years with unicentric invasive or in situ tumors ≤3.0 cm with positive estrogen or progesterone receptors and no metastasis to axillary nodes that have been excised with negative margins. Strict dosimetric parameters were required to be met before acceptance into the trial.

Results: A group of 200 patients was prospectively enrolled and followed for a minimum of 6 months. Two- or 3-day brachytherapy was associated with low acute or subacute toxicity, 97.25% excellent or good cosmetic outcomes, and excellent local control in select breast cancers.

Conclusions: Ultrashort breast brachytherapy is dosimetrically feasible and can be delivered with excellent short-term tolerance and low toxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2018.12.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373303PMC
May 2019

Insurance Approval for Proton Beam Therapy and its Impact on Delays in Treatment.

Int J Radiat Oncol Biol Phys 2019 07 14;104(4):714-723. Epub 2018 Dec 14.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Electronic address:

Purpose: Prior authorization (PA) has been widely implemented for proton beam therapy (PBT). We sought to determine the association between PA determination and patient characteristics, practice guidelines, and potential treatment delays.

Methods And Materials: A single-institution retrospective analysis was performed of all patients considered for PBT between 2015 and 2018 at a National Cancer Institute-designated Comprehensive Cancer Center. Differences in treatment start times and denial rates over time were compared, and multivariable logistic regression was used to identify predictors of initial denial.

Results: A total of 444 patients were considered for PBT, including 396 adult and 48 pediatric patients. The American Society for Radiation Oncology model policy supported PBT coverage for 77% of the cohort. Of adult patients requiring PA, 64% were initially denied and 32% remained denied after appeal. In patients considered for reirradiation or randomized phase 3 trial enrollment, initial denial rates were 57% and 64%, respectively. Insurance coverage was not related to diagnosis, reirradiation, trial enrollment, or the American Society for Radiation Oncology model policy guidelines, but it was related to insurance category on multivariable analysis (P < .001). Over a 3-year timespan, initial denial rates increased from 55% to 74% (P = .034). PA delayed treatment start by an average of 3 weeks (and up to 4 months) for those requiring appeal (P < .001) and resulted in 19% of denied patients abandoning radiation treatment altogether. Of pediatric patients, 9% were initially denied, all of whom were approved after appeal, and PA requirement did not delay treatment start (P = .47).

Conclusions: PA requirements in adults represent a significant burden in initiating PBT and cause significant delays in patient care. Insurance approval is arbitrary and has become more restrictive over time, discordant with national clinical practice guidelines. Payors and providers should seek to streamline coverage policies in alignment with established guidelines to ensure appropriate and timely patient care.
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http://dx.doi.org/10.1016/j.ijrobp.2018.12.021DOI Listing
July 2019

VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells.

Oncotarget 2018 May 25;9(40):25833-25841. Epub 2018 May 25.

Department of Radiation Oncology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

Purpose: DNA double-strand breaks (DSBs) can be repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). We demonstrate the selectivity of VX-984, a DNA-PK inhibitor, using assays not previously reported.

Experimental Design: The class switch recombination assay (CSR) in primary B cells was used to measure efficiency of NHEJ. A cellular reporter assay (U2OS EJ-DR) was used to assess the efficiency of HR and NHEJ in cells treated with VX-984. Immunofluorescence assays (IF) evaluated γ-H2AX foci for DSB repair kinetics in human astrocytes and T98G glioma cells. Western blotting was used to evaluate phosphorylation of DNA-PKcs substrates.

Results: We found a dose-dependent reduction in CSR efficiency with VX-984, and through the EJ-DR assay, dramatic dose-dependent increases in HR and mNHEJ. Immunofluorescence assays showed an inability of malignant cells to resolve γ-H2AX foci in the presence of VX-984. Radiation-induced phosphorylation of DNA-PK substrates was further reduced by treatment with VX-984.

Conclusions: VX-984 efficiently inhibits NHEJ, resulting in compensatory increases in alternative repair pathways, increases DSBs, and appears to affect transformed cells preferentially.
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http://dx.doi.org/10.18632/oncotarget.25383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995231PMC
May 2018

Breast-conservation Therapy After Neoadjuvant Chemotherapy Does Not Compromise 10-Year Breast Cancer-specific Mortality.

Am J Clin Oncol 2018 12;41(12):1246-1251

Departments of Radiation Oncology.

Objectives: Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery by downstaging disease in patients with breast cancer. The aim of this study was to determine whether patients who received neoadjuvant chemotherapy have equal survival after breast-conservation therapy compared with mastectomy.

Material And Methods: Using the New Jersey State Cancer Registry (NJSCR) patients with a primary breast cancer diagnosed between 1998 and 2003 who underwent neoadjuvant chemotherapy were selected (n=1,468). Of those, only patients who received lumpectomy plus radiation (n=276) or mastectomy without radiation (n=442) were included in the analysis. The main outcome measured included 10-year breast cancer-specific mortality, with 90% of patients with known vital status through the end of 2011.

Results: Baseline characteristics did not differ significantly between the breast-conservation and mastectomy without radiation groups except with respect to summary stage and lymph node involvement. After propensity score matching these differences were no longer statistically significant; however, both estrogen and progesterone status achieved statistical significance. The Kaplan-Meier survival curve showed that the breast-conservation group had significantly higher breast cancer-specific survival than the mastectomy group (P=0.0046). After adjusting for the propensity score in the regression model, the breast-conservation group continued to show significantly better survival than the mastectomy group (hazard ratios, 0.46; 95% confidence interval, 0.27-0.78).

Conclusions: This study is consistent with previous research showing that breast-conserving surgery after neoadjuvant chemotherapy does not reduce breast cancer-specific survival. In fact, patients undergoing breast-conservation after neoadjuvant therapy appeared to have better survival than patients undergoing mastectomy without radiation.
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http://dx.doi.org/10.1097/COC.0000000000000456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077450PMC
December 2018

Mortality After Stereotactic Radiosurgery for Brain Metastases and Implications for Optimal Utilization: A National Cancer Database Study.

Am J Clin Oncol 2018 Nov;41(11):1142-1147

*Northwestern University Feinberg School of Medicine ‡Department of Radiation Oncology, Northwestern Memorial Hospital §Department of Radiation and Cellular Oncology, Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL †Memorial Sloan Kettering Cancer Center, New York, NY.

Objectives: Brain metastases are associated with cancer progression and poor outcomes. The use of stereotactic radiosurgery (SRS) to treat brain metastases has been increasing due to its potential to quickly treat metastatic disease while avoiding the morbidity associated with surgery or whole brain radiation therapy (WBRT). This study seeks to analyze practice patterns of the use of SRS for brain metastases, focusing on the endpoint of short-term mortality.

Materials And Methods: This study used the National Cancer Database to observe cancer patients diagnosed with a non-Central Nervous System primary from 2010 to 2012 who presented at diagnosis with metastatic disease to the brain and received either WBRT or SRS. The primary endpoint was time to mortality determined by the Kaplan-Meier product-limit estimate of the failure function.

Results: A total of 18,604 patients were included in the analysis from first day of treatment (16,219 patients received WBRT and 2385 received SRS). At 90 days, mortality was 39.3% for those who received WBRT and 20.0% for those who received SRS. For patients 70 and older who received SRS, mortality was 30.2% at 90 days.

Conclusions: Analysis of short-term mortality after treatment for brain metastases by using the National Cancer Database provides a window into national treatment patterns and associated outcomes. Roughly 1 in 5 patients who receive SRS and roughly 1 in 3 patients 70 and older who receive SRS die within 90 days of treatment. These data suggest some degree of overutilization of SRS in some patient populations, most notably those patients over the age of 70.
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http://dx.doi.org/10.1097/COC.0000000000000441DOI Listing
November 2018
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