Publications by authors named "Abraham J Wu"

94 Publications

Next-Generation Sequencing of 487 Esophageal Adenocarcinomas Reveals Independently Prognostic Genomic Driver Alterations and Pathways.

Clin Cancer Res 2021 Apr 1. Epub 2021 Apr 1.

Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center.

Purpose: To delineate recurrent oncogenic driver alterations and dysregulated pathways in esophageal adenocarcinoma and to assess their prognostic value.

Experimental Design: We analyzed a large cohort of patients with lower esophageal and junctional adenocarcinoma, prospectively sequenced by MSK-IMPACT with high-quality clinical annotation. Patients were subdivided according to treatment intent, curative vs. palliative, which closely mirrored clinical staging. Genomic features, alterations, and pathways were examined for association with overall survival using Cox proportional hazard models, adjusted for relevant clinicopathologic factors knowable at the time of diagnosis.

Results: Analysis of 487 patients revealed 16 oncogenic driver alterations, mostly amplifications, present in {greater than or equal to}5% of patients. Patients in the palliative-intent cohort, compared to those in the curative-intent cohort, were more likely to have metastatic disease, amplifications, Cell Cycle and RTK-RAS pathway alterations, as well as a higher fraction of genome altered and rate of whole-genome doubling. In multivariable analyses, alterations, alterations, amplifications, Cell Cycle and TGFb pathways, and overall number of oncogenic drivers were independently associated with worse overall survival. amplification was associated with improved survival, presumably due to trastuzumab therapy.

Conclusions: Our study suggests that higher levels of genomic instability are associated with more advanced disease in esophageal adenocarcinoma. Furthermore, , , and represent prognostic biomarkers, given their strong association with poor survival.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4707DOI Listing
April 2021

Genomic Analyses for Predictors of Response to Chemoradiation in Stage III Non-Small Cell Lung Cancer.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100615. Epub 2020 Nov 14.

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

Background: Radiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy.

Methods: We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing.

Results: 110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7, = .003 and = .003, respectively). Analyses restricted to loss-of-function mutations identified and deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, < .001 and < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, = .049).

Conclusions: This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in and as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.
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http://dx.doi.org/10.1016/j.adro.2020.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897765PMC
November 2020

Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair-proficient Metastatic Colorectal Cancer.

Clin Cancer Res 2021 Jan 27. Epub 2021 Jan 27.

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

Purpose: Immune checkpoint inhibition (ICI) alone is not active in mismatch repair-proficient (MMR-P) metastatic colorectal cancer (mCRC), nor does radiotherapy alone result in objective systemic benefit. However, combined radiotherapy plus ICI can induce systemic antitumor immunity in preclinical and clinical models.

Patients And Methods: In this single-center, phase II study, patients with chemotherapy-refractory MMR-P mCRC received durvalumab 1,500 mg plus tremelimumab 75 mg every 4 weeks plus radiotherapy. The primary endpoint was objective response rate (ORR) in nonirradiated lesions. Treatment and efficacy were correlated with peripheral immune cell profiles.

Results: We enrolled 24 patients, and report outcomes after a median follow-up of 21.8 (range: 15.9-26.3) months. The ORR was 8.3% (2 patients) [95% confidence interval (CI), 1.0-27.0]. The median progression-free survival was 1.8 (95% CI, 1.7-1.9) months, median overall survival was 11.4 (95% CI, 10.1-17.4) months. Twenty five percent of patients ( = 6) had treatment-related grade 3-4 adverse events. We observed increased circulating CD8 T lymphocyte activation, differentiation, and proliferation in patients with objective response.

Conclusion: This combination of radiotherapy plus ICI study did not meet the prespecified endpoint criteria to be considered worthwhile for further study. However, rare instances of systemic immune augmentation and regression in nonirradiated lesions were observed (an abscopal response). Combination durvalumab and tremelimumab plus radiotherapy is feasible in MMR-P mCRC with a manageable safety profile. Further studies of novel immunotherapy combinations, and identification of biomarkers predictive of abscopal response are warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2474DOI Listing
January 2021

Survival Following Trimodality Therapy in Patients With Locally Advanced Esophagogastric Adenocarcinoma: Does Only a Complete Pathologic Response Matter?

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NW 10065.

Objective: To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival.

Summary Background Data: pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint.

Methods: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis.

Results: Among 788 patients, median follow-up was 37.5 months (range, 0.4-210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival (P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR.

Conclusions: ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to ≥90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to ≥90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.
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http://dx.doi.org/10.1097/SLA.0000000000004638DOI Listing
November 2020

A More Extensive Lymphadenectomy Enhances Survival Following Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Adenocarcinoma.

Ann Surg 2020 Nov 12. Epub 2020 Nov 12.

Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Objective: We sought to determine the extent of lymphadenectomy that optimizes staging and survival in patients with locally advanced esophageal adenocarcinoma (EAC) treated with neoadjuvant chemoradiotherapy followed by esophagectomy.

Summary Background Data: Several studies have found that a more extensive lymphadenectomy leads to better disease-specific survival in patients treated with surgery alone. Few studies, however, have investigated whether this association exists for patients treated with neoadjuvant chemoradiotherapy.

Methods: We examined our prospective database and identified patients with EAC treated with neoadjuvant chemoradiotherapy followed by esophagectomy between 1995 and 2017. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier methods, and a multivariable Cox proportional hazards model was used to identify independent predictors of OS and DFS. The relationship between the total number of nodes removed and 5-year OS or DFS was plotted using restricted cubic spline functions.

Results: In total, 778 patients met the inclusion criteria. The median number of excised nodes was 21 (interquartile range, 16-27). A lower number of excised lymph nodes was independently associated with worse OS and DFS (OS: hazard ratio [HR], 0.98; confidence interval [CI], 0.97-1.00; P = 0.013; DFS: HR, 0.99; CI, 0.98-1.00; P = 0.028). Removing 25 to 30 lymph nodes was associated with a 10% risk of missing a positive lymph node. Both OS and DFS improved with up to 20 to 25 lymph nodes removed, regardless of treatment response.

Conclusions: The optimal extent of lymphadenectomy to enhance both staging and survival following chemoradiotherapy, regardless of treatment response, is approximately 25 lymph nodes.
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http://dx.doi.org/10.1097/SLA.0000000000004479DOI Listing
November 2020

Clinical and Dosimetric Predictors of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation Therapy.

Pract Radiat Oncol 2021 Jan-Feb;11(1):e52-e62. Epub 2020 Oct 14.

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

Purpose: Radiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiation therapy. Data sets reporting RP rates after postoperative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era.

Methods And Materials: We reviewed 285 patients with non-small cell lung cancer treated with PORT at our institution from May 2004 to January 2017. Complete dosimetric data and clinical records were reviewed and analyzed with grade 2 or higher RP as the endpoint (RP2+) (Common Terminology Criteria for Adverse Events v4.0). Patients were a median of 67 years old (range, 28-87), and most had pathologic stage III non-small cell lung cancer (91%) and received trimodality therapy (90%). Systematic dosimetric analyses using Dx increments of 5% and Vx increments of 2 Gy were performed to robustly evaluate dosimetric variables. Lung V was also evaluated.

Results: The incidence of RP2+ after PORT was 12.6%. Dosimetric factors most associated with RP2+ were total lungV (hazard ratio [HR] 1.04, P < .001) and heart V (HR 1.03, P = .001). On univariate analysis, the clinical factors of age (HR 1.05, P = .006) and carboplatin chemotherapy (HR 2.32, P = .012) were correlated with RP2+. On step-up multivariate analysis, only bivariate models remained significant, including lungV (HR 1.037, P < .001) and age (HR 1.052, P = .011).

Conclusions: The incidence of RP after PORT is consistent with the literature. Factors correlated with RP include lung and heart doses, age, and carboplatin chemotherapy. These data also suggest that elderly patients may be more susceptible to lower doses of radiation to the lung. Based on these data, dose constraints to limit the risk of RP2+ to <5% in the setting of PORT include lungV ≤65% in patients <65 years old and lungV ≤36% in patients 65 years or older.
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http://dx.doi.org/10.1016/j.prro.2020.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785592PMC
October 2020

Predictive Modeling of Thoracic Radiotherapy Toxicity and the Potential Role of Serum Alpha-2-Macroglobulin.

Front Oncol 2020 6;10:1395. Epub 2020 Aug 6.

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

To investigate the impact of alpha-2-macroglobulin (A2M), a suspected intrinsic radioprotectant, on radiation pneumonitis and esophagitis using multifactorial predictive models. Baseline A2M levels were obtained for 258 patients prior to thoracic radiotherapy (RT). Dose-volume characteristics were extracted from treatment plans. Spearman's correlation (Rs) test was used to correlate clinical and dosimetric variables with toxicities. Toxicity prediction models were built using least absolute shrinkage and selection operator (LASSO) logistic regression on 1,000 bootstrapped datasets. Grade ≥2 esophagitis and pneumonitis developed in 61 (23.6%) and 36 (14.0%) patients, respectively. The median A2M level was 191 mg/dL (range: 94-511). Never/former/current smoker status was 47 (18.2%)/179 (69.4%)/32 (12.4%). We found a significant negative univariate correlation between baseline A2M levels and esophagitis (Rs = -0.18/ = 0.003) and between A2M and smoking status (Rs = 0.13/ = 0.04). Further significant parameters for grade ≥2 esophagitis included age (Rs = -0.32/ < 0.0001), chemotherapy use (Rs = 0.56/ < 0.0001), dose per fraction (Rs = -0.57/ < 0.0001), total dose (Rs = 0.35/ < 0.0001), and several other dosimetric variables with Rs > 0.5 ( < 0.0001). The only significant non-dosimetric parameter for grade ≥2 pneumonitis was sex (Rs = -0.32/ = 0.037) with higher risk for women. For pneumonitis D15 (lung) (Rs = 0.19/ = 0.006) and D45 (heart) (Rs = 0.16/ = 0.016) had the highest correlation. LASSO models applied on the validation data were statistically significant and resulted in areas under the receiver operating characteristic curve of 0.84 (esophagitis) and 0.78 (pneumonitis). Multivariate predictive models did not require A2M to reach maximum predictive power. This is the first study showing a likely association of higher baseline A2M values with lower risk of radiation esophagitis and with smoking status. However, the baseline A2M level was not a significant risk factor for radiation pneumonitis.
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http://dx.doi.org/10.3389/fonc.2020.01395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423838PMC
August 2020

Analysis of pneumonitis and esophageal injury after stereotactic body radiation therapy for ultra-central lung tumors.

Lung Cancer 2020 09 8;147:45-48. Epub 2020 Jul 8.

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

Objectives: SBRT has been associated with serious toxicity in ultra-central lung tumors, but little is known about the incidence and dosimetric correlates of pulmonary and esophageal complications in this setting.

Materials And Methods: We retrospectively reviewed SBRT patients whose lung tumor abutted proximal airways, or whose planning target volume overlapped esophagus. All patients received 5-15 fractions of high-dose, image-guided radiation. The primary endpoint was SBRT-related toxicity, with local control and survival as secondary endpoints.

Results: We included 88 patients. Nineteen patients (22 %) experienced grade ≥3 (G3+) toxicity, including 6 cases of G3+ radiation pneumonitis and 4 cases of G3+ esophageal injury. Two patients developed trachea-esophageal fistula. Overall incidence of radiation pneumonitis was 23 %. Ten patients (11.4 %) succumbed to SBRT-related complications. Multiple dosimetric parameters for lung (including mean lung dose and V20) and esophagus (including maximum point dose) correlated with radiation pneumonitis and esophageal toxicity, respectively. No impact of fractionation on toxicity was seen.

Conclusion: This analysis indicates that high rate and multiple manifestations of pulmonary and esophageal toxicity occur after SBRT for ultra-central tumors. In particular, severe radiation pneumonitis and tracheoesophageal fistula are possible. Dosimetric parameters such as mean lung dose and maximum esophageal dose are significantly correlated with toxicity. Further study is needed to optimize the safe delivery of SBRT in these patients.
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http://dx.doi.org/10.1016/j.lungcan.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484437PMC
September 2020

Need for Caution in the Diagnosis of Radiation Pneumonitis During the COVID-19 Pandemic.

Adv Radiat Oncol 2020 Jul-Aug;5(4):617-620. Epub 2020 May 5.

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

Purpose: Patients with cancer are at high risk for mortality from coronavirus disease 2019 (COVID-19). Radiation pneumonitis (RP) is a common toxicity of thoracic radiation therapy with clinical and imaging features that overlap with those of COVID-19; however, RP is treated with high-dose corticosteroids, which may exacerbate COVID-19-associated lung injury. We reviewed patients who presented with symptoms of RP during the intensification of a regional COVID-19 epidemic to report on their clinical course and COVID-19 testing results.

Methods And Materials: The clinical course and chest computed tomography (CT) imaging findings of consecutive patients who presented with symptoms of RP in March 2020 were reviewed. The first regional COVID-19 case was diagnosed on March 1, 2020. All patients underwent COVID-19 qualitative RNA testing.

Results: Four patients with clinical suspicion for RP were assessed. Three out of 4 patients tested positive for COVID-19. All patients presented with symptoms of cough and dyspnea. Two patients had a fever, of whom only 1 tested positive for COVID-19. Two patients started on an empirical high-dose corticosteroid taper for presumed RP, but both had clinical deterioration and ultimately tested positive for COVID-19 and required hospitalization. Chest CT findings in patients suspected of RP but ultimately diagnosed with COVID-19 showed ground-glass opacities mostly pronounced outside the radiation field.

Conclusions: As this pandemic continues, patients with symptoms of RP require diagnostic attention. We recommend that patients suspected of RP be tested for COVID-19 before starting empirical corticosteroids and for careful attention to be paid to chest CT imaging to prevent potential exacerbation of COVID-19 in these high-risk patients.
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http://dx.doi.org/10.1016/j.adro.2020.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199721PMC
May 2020

Radiation pneumonitis in lung cancer patients treated with chemoradiation plus durvalumab.

Cancer Med 2020 07 6;9(13):4622-4631. Epub 2020 May 6.

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

Introduction: Durvalumab after concurrent chemoradiation (cCRT) is now standard of care for unresected stage III non-small cell lung cancer (NSCLC). However, there is limited data on radiation pneumonitis (RP) with this regimen. Therefore, we assessed RP and evaluated previously validated toxicity models in predicting for RP in patients treated with cCRT and durvalumab.

Methods: Patients treated with cCRT and ≥ 1 dose of durvalumab were evaluated to identify cases of ≥ grade 2 RP. The validity of previously published RP models was assessed in this cohort as well a reference cohort treated with cCRT alone. The timing and incidence of RP was compared between cohorts.

Results: In total, 11 (18%) of the 62 patients who received cCRT and durvalumab developed ≥ grade 2 RP a median of 3.4 months after cCRT. The onset of RP among patients treated with cCRT and durvalumab was significantly longer vs the reference cohort (3.4 vs 2.1 months; P = .01). Numerically more patients treated with cCRT and durvalumab developed RP than patients in the reference cohort (18% vs 9%, P = .09). Among patients treated with cCRT and durvalumab, 82% (n = 9) were responsive to treatment with high-dose glucocorticoids. Previously published RP models widely underestimated the rate of RP in patients treated with cCRT and durvalumab [AUC ~ 0.50; p(Hosmer-Lemeshow): 0.98-1.00].

Conclusions: Our data suggest a delayed onset of RP in patients treated with cCRT and durvalumab vs cCRT alone, and for RP to develop in a greater number of patients treated with cCRT and durvalumab. Previously published RP models significantly underestimate the rate of symptomatic RP among patients treated with cCRT and durvalumab.
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http://dx.doi.org/10.1002/cam4.3113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333832PMC
July 2020

Clinical outcomes, local-regional control and the role for metastasis-directed therapies in stage III non-small cell lung cancers treated with chemoradiation and durvalumab.

Radiother Oncol 2020 08 30;149:205-211. Epub 2020 Apr 30.

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

Background And Purpose: Concurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined.

Materials And Methods: We reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local-regional and metastatic failures.

Results: Sixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51-79%) and 85% (95% CI: 75-95%), respectively. The cumulative 12-month incidence of local-regional and distant failures were 18% (95% CI: 5.9-30%) and 30% (95% CI: 16.3-44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS.

Conclusions: Outcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone.
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http://dx.doi.org/10.1016/j.radonc.2020.04.047DOI Listing
August 2020

Patterns and Perceptions of "Away" Rotations Among Radiation Oncology Residency Applicants.

Int J Radiat Oncol Biol Phys 2020 08 23;107(5):1007-1011. Epub 2020 Apr 23.

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

Purpose: Medical students often complete clinical rotations at other institutions (away rotations). This study assesses the number of away rotations undertaken by radiation oncology residency applicants and their value from the applicants' perspective.

Methods And Materials: A survey was sent to applicants to a single radiation oncology program from 2015 to 2017. Questions addressed away rotation frequency, funding, motivations, barriers, and match results. A χ test was used to assess the correlation between number of away rotations and matching to an away program. Binary logistic regression was used to assess factors associated with undertaking >2 away rotations.

Results: The response rate was 39% (n = 194); 89% of respondents completed ≥1 away rotation (median, 2; interquartile range, 2-3), of whom 39% (n = 67) matched to an away program. The number of away rotations completed did not differ between those who did and did not match (P = .29). Furthermore, the number of away rotations did not correlate with matching at an away program (P = .40). Factors associated with completing more away rotations included male sex and high loan burden (P < .05). Away rotations were perceived as extremely important (71%), with interest in a specific program (44%) and obtaining letters of recommendation (31%) the most common reasons to pursue away rotations. Only 9% (n = 15) of applicants did away rotations because they had no home program. Funding sources included personal savings (29%), family support (26%), and loans (22%). If costs were inconsequential, 67 applicants (35%) noted they would do more away rotations.

Conclusions: Away rotations are common and often result in students matching to an away program, although benefits of ≥2 away rotations appear limited and have associated costs. Limiting the number of away rotations in radiation oncology may decrease costs without sacrificing one's chances of matching.
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http://dx.doi.org/10.1016/j.ijrobp.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381360PMC
August 2020

Management of Locally Advanced Rectal Cancer During The COVID-19 Pandemic: A Necessary Paradigm Change at Memorial Sloan Kettering Cancer Center.

Adv Radiat Oncol 2020 Jul-Aug;5(4):687-689. Epub 2020 Apr 22.

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

The COVID-19 pandemic will consume significant health care resources. Given the concerns for rapidly increasing infection rates in the United States, impending staffing shortages, and the potential for resource reallocation, we rapidly reevaluated our rectal cancer practice policies during this public health emergency. Before the pandemic, we commonly used total neoadjuvant therapy with a strong preference for long-course chemoradiation. In the setting of the ongoing pandemic, we now mandate short-course radiation therapy (SCRT). Despite multiple randomized trials demonstrating no difference in locoregional recurrence, distant recurrence, or overall survival between SCRT and long-course chemoradiation, the adaptation of SCRT in the United States has been low given concerns for less tumor downstaging and increased toxicity. In the setting of the ongoing and likely prolonged COVID-19 pandemic, we feel that these concerns must be reevaluated, because SCRT presents a well-validated alternative that will allow us to meet the needs of a greater number of potentially curable patients at a time when resources are severely and acutely constrained.
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http://dx.doi.org/10.1016/j.adro.2020.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175910PMC
April 2020

Thoracic Radiation Therapy During Coronavirus Disease 2019: Provisional Guidelines from a Comprehensive Cancer Center within a Pandemic Epicenter.

Adv Radiat Oncol 2020 Jul-Aug;5(4):603-607. Epub 2020 Apr 20.

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

Coronavirus disease 2019 is an unprecedented pandemic with significant and evolving impact on the practice of radiation oncology. Radiation oncology departments must anticipate and account for coronavirus disease 2019 exposure risk for both patients and staff. The potential for severe radiation therapy resource constraints, particularly due to staff illness, must also be considered. Here we present provisional guidelines for thoracic radiation therapy adopted at our facility, a high-volume cancer center located in a United States pandemic epicenter. Generally, these guidelines reflect the principle that where evidence-supported hypofractionated schedules with comparable efficacy and toxicity exist, the shortest such schedules should be employed. In addition, we discuss potential adaptations in the prioritization and timing of radiation therapy for thoracic malignancies under these circumstances.
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http://dx.doi.org/10.1016/j.adro.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169880PMC
April 2020

Radiation Therapy for Small Cell Lung Cancer: An ASTRO Clinical Practice Guideline.

Pract Radiat Oncol 2020 May - Jun;10(3):158-173. Epub 2020 Mar 23.

Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY. Electronic address:

Purpose: Several sentinel phase III randomized trials have recently been published challenging traditional radiation therapy (RT) practices for small cell lung cancer (SCLC). This American Society for Radiation Oncology guideline reviews the evidence for thoracic RT and prophylactic cranial irradiation (PCI) for both limited-stage (LS) and extensive-stage (ES) SCLC.

Methods: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications, dose fractionation, techniques and timing of thoracic RT for LS-SCLC, the role of stereotactic body radiation therapy (SBRT) compared with conventional RT in stage I or II node negative SCLC, PCI for LS-SCLC and ES-SCLC, and thoracic consolidation for ES-SCLC. Recommendations were based on a systematic literature review and created using a consensus-building methodology and system for grading evidence quality and recommendation strength.

Results: The task force strongly recommends definitive thoracic RT administered once or twice daily early in the course of treatment for LS-SCLC. Adjuvant RT is conditionally recommended in surgically resected patients with positive margins or nodal metastases. Involved field RT delivered using conformal advanced treatment modalities to postchemotherapy volumes is also strongly recommended. For patients with stage I or II node negative disease, SBRT or conventional fractionation is strongly recommended, and chemotherapy should be delivered before or after SBRT. In LS-SCLC, PCI is strongly recommended for stage II or III patients who responded to chemoradiation, conditionally not recommended for stage I patients, and should be a shared decision for patients at higher risk of neurocognitive toxicities. In ES-SCLC, radiation oncologist consultation for consideration of PCI versus magnetic resonance surveillance is strongly recommended. Lastly, the use of thoracic RT is strongly recommended in select patients with ES-SCLC after chemotherapy treatment, including a conditional recommendation in those responding to chemotherapy and immunotherapy.

Conclusions: RT plays a vital role in both LS-SCLC and ES-SCLC. These guidelines inform best clinical practices for local therapy in SCLC.
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http://dx.doi.org/10.1016/j.prro.2020.02.009DOI Listing
December 2020

Delivering safe and effective stereotactic body radiation therapy for patients with centrally located early stage non-small cell lung cancer.

Chin Clin Oncol 2020 06 15;9(3):39. Epub 2020 Jan 15.

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

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http://dx.doi.org/10.21037/cco.2019.12.17DOI Listing
June 2020

Utilization and factors precluding the initiation of consolidative durvalumab in unresectable stage III non-small cell lung cancer.

Radiother Oncol 2020 03 28;144:101-104. Epub 2019 Nov 28.

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

Durvalumab after concurrent chemoradiation has significantly improved survival in stage III non-small cell lung cancer (NSCLC). However, there is limited data evaluating the utilization and challenges to deliver durvalumab consolidation in the real world. We assessed the use of consolidative durvalumab at a large academic center to examine clinical limitations to delivery of this practice-changing regimen. We found that despite incorporating consolidative durvalumab into standard practice for stage III unresectable NSCLC, 27% patients did not initiate this treatment, largely due to disease progression or toxicity from chemoradiation.
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http://dx.doi.org/10.1016/j.radonc.2019.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523024PMC
March 2020

The Current Situation of Esophageal Cancer Staging and Perioperative Strategies Determination in Central and Southern China: A Cross Sectional Survey.

Front Oncol 2019 22;9:1098. Epub 2019 Oct 22.

Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

We aim to investigate the current esophageal cancer staging according to the 7th edition TNM classification for esophageal carcinoma proposed by American Joint Committee on Cancer (AJCC) among oncology-related physicians in China. A specifically-designed 14-item questionnaire was distributed to 366 doctors who were working with esophageal cancer patients. We collected and analyzed the feedbacks and explored the possible associations within different departments, including thoracic surgery, the internal medicine of gastroenterology, oncology, and/ radiotherapy in eight different hospitals from central and southern China. Among all the responses, 31.42% of them were from thoracic surgery department, 40.44% were from oncology and/or radiation therapy and 28.14% were from the internal medicine of gastroenterology, respectively. Surprisingly, in total 66.12% of all the physicians were unaware that the 7th edition of esophageal carcinoma TNM classification was released in 2009; only 21.86 and 16.67% of physicians recognized cervical nodes and celiac nodes as regional lymph nodes. Furthermore, 67.21% physicians didn't know that tumor location, histologic grade, and histopathology were accepted as new prognostic factors in the latest TNM system; and 51.37% physicians could not determine the correct TNM classification of esophagogastric junction cancers. Intriguingly, over 50% of them could still design appropriate perioperative strategies. The 7th edition of the TNM classification for esophageal carcinoma is poorly recognized and understood in central and southern China, which might contribute to the relatively low rates of appropriate perioperative procedures applied for esophageal cancer patients.
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http://dx.doi.org/10.3389/fonc.2019.01098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817579PMC
October 2019

Are unsatisfactory outcomes after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer due to treatment-related immunosuppression?

Radiother Oncol 2020 02 12;143:51-57. Epub 2019 Oct 12.

Dept of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.

Background And Purpose: We test the hypothesis that unsatisfactory outcomes after concurrent chemoradiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC) are due to treatment-related immunosuppression.

Materials And Methods: White blood cells (WBCs) data were retrospectively collected for all stage IIIA/B LA-NSCLC patients before and after (after RT: two weeks, two months, four months) concurrent chemotherapy and intensity-modulated RT in which patients were treated to a median of 63 Gy (1.8-2.0 Gy/fractions) in 2004-2014 (N = 155). Nine WBC variables were generated from pre-RT normalized absolute number of lymphocytes and neutrophils (L, N) and the N/L thereof. A WBC variable was considered a predictor for overall survival and recurrence (distant/local/nodal/regional) if p ≤ 0.006 (corrected for 9 variables) from Cox regression and competing risk analyses, respectively; both conducted using bootstrap resampling. Finally, a WBC variable predicting any of the outcomes was linearly associated with each of eleven disease/patient/treatment characteristics (p ≤ 0.005; corrected for 11 characteristics).

Results: At the three post-RT time points both L and N significantly decreased (p < 0.0003). Overall survival was associated with N and N/L four months post-RT (p = 0.00001, 0.0003); regional recurrence was associated with L two months post-RT (p < 0.0001). None of the disease/patient/treatment characteristics was significantly associated with any of the three WBC variables that predicted OS or recurrence (lowest p-value: p = 0.006 for tumour stage,).

Conclusion: Significantly lower WBC levels after concurrent chemo-RT for LA-NSCLC are associated with worse long-term outcomes. The mechanism behind this treatment-related immunosuppression requires further analysis likely including other characteristics as no statistically significant association was established between any WBC variable and the disease/patient/treatment characteristics.
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http://dx.doi.org/10.1016/j.radonc.2019.07.016DOI Listing
February 2020

Hypofractionated vs. conventional radiation therapy for stage III non-small cell lung cancer treated without chemotherapy.

Acta Oncol 2020 Feb 12;59(2):164-170. Epub 2019 Oct 12.

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

Patients with unresectable locally advanced NSCLC who refuse or are not candidates for chemotherapy often receive radiation therapy (RT) alone. Hypofractionated RT (HFRT) regimens are becoming increasingly common. An analysis of the National Cancer Database (NCDB) was performed to evaluate the practice patterns and outcomes of HFRT vs. conventionally fractionated RT (CFRT) in patients with stage III NSCLC undergoing definitive RT alone. The NCDB was queried for all patients with stage III NSCLC diagnosed between 2004 and 2014 who received RT alone. CFRT was defined as patients treated to a total dose of 60-80 Gy in 1.8-2 Gy daily fractions. HFRT was defined as patients treated to a total dose of 50-80 Gy in 2.25-4 Gy fractions. Logistic regression, univariable and multivariable analyses (MVAs) for overall survival (OS) and propensity score matched analyses (PSMAs) were performed. A total of 6490 patients were evaluated: 5378 received CFRT and 1112 received HFRT. Median CFRT dose was 66 Gy in 2 Gy fractions vs. 58.5 Gy in 2.5 Gy fractions for HFRT. HFRT was associated with older age, lower biological effective dose (BED), academic facility type, higher T-stage and lower N-stage. On initial analysis, HFRT was associated with inferior OS (median 9.9 vs. 11.1 months, <.001), but after adjusting for the imbalance in covariates such as age, BED, T-stage and N-stage using PSMA, the difference in survival was no longer significant (=.1). In the appropriate clinical context, HFRT can be an option for patients with locally advanced NSCLC who are not candidates for chemotherapy or surgical resection. HFRT needs to be further studied in prospective trials to evaluate toxicity and tumor control.
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http://dx.doi.org/10.1080/0284186X.2019.1675907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493987PMC
February 2020

Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for esophageal squamous cell cancer patients presenting with oligometastases.

J Thorac Dis 2019 Apr;11(4):1536-1545

Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: The potential survival benefits of adding radiotherapy to systemic therapy for esophageal cancer patients with oligometastases are unknown.

Methods: In this retrospective analysis, patients with stage IV esophageal cancer (according to the American Joint Committee on Cancer Seventh edition staging system) with ≤3 metastases who underwent chemotherapy with cisplatin/paclitaxel between 2012 and 2015 were identified. Patients received chemotherapy (CT) alone concurrent chemoradiotherapy (CCRT) to all metastases.

Results: Of 461 patients, 97% had squamous cell cancer. One hundred and ninety-six patients (42.5%) received CCRT and 265 (57.5%) underwent CT alone. At week 8, there were 3 (1.5%) complete responses (CR) and 95 (48.5%) partial responses (PR) in the CCRT group, compared to 3 (1.1%) CR and 102 (38.5%) PR in the CT alone group. The overall rate of improvement in dysphagia score was noted in 78.5% of patients in the CCRT group versus 61.5% in the CT alone group (P=0.014). A statistically significant difference was demonstrated in disease control rate between the two groups (81.6% 64.5%, P<0.001). Patients who underwent CCRT had superior median PFS and a trend toward longer median OS compared to those receiving CT alone (8.7 7.3 months, P=0.002 and 16.8 14.8 months, P=0.056, respectively). The median OS was 19.3 months in patients who achieved CR/PR, compared to 14.9 months and 9.6 months for patients who had stable disease and progressive disease, respectively (P<0.001).

Conclusions: Compared to chemotherapy alone, chemoradiation to all sites in patients with esophageal cancer with ≤3 metastases may lead to a modest increase in PFS and a trend toward longer OS. Further investigation of optimal integration of radiotherapy and chemotherapy in these patients is warranted.
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http://dx.doi.org/10.21037/jtd.2019.03.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531702PMC
April 2019

The American Brachytherapy Society consensus statement on intraoperative radiation therapy.

Brachytherapy 2019 May - Jun;18(3):242-257

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland, OH. Electronic address:

Purpose: Although radiation therapy has traditionally been delivered with external beam or brachytherapy, intraoperative radiation therapy (IORT) represents an alternative that may shorten the course of therapy, reduce toxicities, and improve patient satisfaction while potentially lowering the cost of care. At this time, there are limited evidence-based guidelines to assist clinicians with patient selection for IORT. As such, the American Brachytherapy Society presents a consensus statement on the use of IORT.

Methods: Physicians and physicists with expertise in intraoperative radiation created a site-directed guideline for appropriate patient selection and utilization of IORT.

Results: Several IORT techniques exist including radionuclide-based high-dose-rate, low-dose-rate, electron, and low-energy electronic. In breast cancer, IORT as monotherapy should only be used on prospective studies. IORT can be considered in the treatment of sarcomas with close/positive margins or recurrent sarcomas. IORT can be considered in conjunction with external beam radiotherapy for retroperitoneal sarcomas. IORT can be considered for colorectal malignancies with concern for positive margins and in the setting of recurrent gynecologic cancers. For thoracic, head and neck, and central nervous system malignancies, utilization of IORT should be evaluated on a case-by-case basis.

Conclusions: The present guidelines provide clinicians with a summary of current data regarding IORT by treatment site and guidelines for the appropriate patient selection and safe utilization of the technique. High-dose-rate, low-dose-rate brachytherapy methods are appropriate when IORT is to be delivered as are electron and low-energy based on the clinical scenario.
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http://dx.doi.org/10.1016/j.brachy.2019.01.015DOI Listing
December 2019

Mind the Gap: An Analysis of "Gap Year" Prevalence, Productivity, and Perspectives Among Radiation Oncology Residency Applicants.

Int J Radiat Oncol Biol Phys 2019 06 11;104(2):456-462. Epub 2019 Feb 11.

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

Purpose: Medical students may take a year off during medical school (a "gap year") to strengthen their applications for competitive specialties such as radiation oncology. This can incur significant financial and opportunity costs. We sought to understand the prevalence, nature, and funding of gap years undertaken by radiation oncology applicants.

Methods And Materials: An anonymous survey was emailed to all applicants to a single radiation oncology program from 2015 to 2017. Survey questions assessed gap year utilization, funding, motivations, and perceptions. Separately, all 2017 Electronic Residency Application Service (n = 176) applications to this program were reviewed for reference.

Results: The 2017 cohort had a response rate of 69% (n = 121), with an overall response rate of 39% (n = 194) for applicants between 2015 to 2017. Of non-MD/PhD respondents, 33% (n = 53) reported taking a gap year. The main reason for a gap year (68%) was to produce more publications, and 50% of all respondents viewed a gap year as "important" or "very important" for matching in radiation oncology. Twenty-eight students (53%) reported using personal loans, savings, or family support to cover gap year expenses. Most who took a gap year (83%) viewed funding as "difficult" or "extremely difficult" to obtain. Fewer publications before gap year and more dedicated research time were significant predictors of undertaking a gap year, whereas sex, marital status, dependent status, and financial aid were not significant.

Conclusions: Research productivity is commonly perceived as important for matching in radiation oncology, leading many applicants to take gap years, which are usually supported by personal financial resources. We did not identify statistically significant socioeconomic disparities between applicants that took a gap year and those who did not. However, further study is warranted to determine whether pressure to take a gap year, particularly in the absence of readily available funding sources, deters some potential applicants from pursuing radiation oncology altogether.
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http://dx.doi.org/10.1016/j.ijrobp.2019.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525797PMC
June 2019

Outcomes of Stage III NSCLC with occult primary vs. known primary lesions.

Lung Cancer 2019 01 17;127:34-36. Epub 2018 Nov 17.

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

Objectives: Occult primary non-small cell lung cancer (OP-NSCLC) involving mediastinal lymph nodes without an identifiable primary tumor is a rare presentation, with little known about how outcomes compare to typical Stage III NSCLC. We reviewed our experience treating OP-NSCLC with definitive radiotherapy and compared outcomes to a contemporary cohort of stage III NSCLC patients.

Materials And Methods: We reviewed 605 patients with stage III NSCLC staged with PET-CT and treated with definitive radiotherapy between 1998 and 2013. Overall survival, intrathoracic control, and freedom from distant metastasis were computed using Kaplan-Meier method and logrank comparison. Cox hazard ratios were used to perform univariate and multivariate analyses.

Results: Twenty-one patients were identified with OP-NSCLC (3.5%). Patients with OP-NSCLC, as compared to known primary NSCLC, had significantly better 5-year rates of intrathoracic control (83.5% vs. 24.2%, P < 0.001), freedom from distant metastasis (59.0% vs. 26.3%, P = 0.003), and overall survival (61.6% vs. 15.2%, P < 0.001). Multivariate analyses confirmed occult primary as an independent prognostic factor associated with a 70% reduction in risk of intrathoracic failure, a 55% reduction in risk of distant metastasis, and a 70% reduction in risk of death.

Conclusion: To our knowledge, this is the largest reported series of OP-NSCLC and the first to compare it to a contemporary cohort of Stage III NSCLC with known primary lesion. Definitive radiation therapy was associated with favorable locoregional control and survival, particularly compared with typical stage III NSCLC. This difference suggests that occult primary NSCLC may be a distinct entity with different biology than typical NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2018.11.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336108PMC
January 2019

Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy.

JAMA Oncol 2019 Apr 11;5(4):e185896. Epub 2019 Apr 11.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: The watch-and-wait (WW) strategy aims to spare patients with rectal cancer unnecessary resection.

Objective: To analyze the outcomes of WW among patients with rectal cancer who had a clinical complete response to neoadjuvant therapy.

Design, Setting, And Participants: This retrospective case series analysis conducted at a comprehensive cancer center in New York included patients who received a diagnosis of rectal adenocarcinoma between January 1, 2006, and January 31, 2015. The median follow-up was 43 months. Data analyses were conducted from June 1, 2016, to October 1, 2018.

Exposures: Patients had a clinical complete response after completing neoadjuvant therapy and agreed to a WW strategy of active surveillance and possible salvage surgery (n = 113), or patients underwent total mesorectal excision and were found to have a pathologic complete response (pCR) at resection (n = 136).

Main Outcomes And Measures: Kaplan-Meier estimates were used for analyses of local regrowth and 5-year rates of overall survival, disease-free survival, and disease-specific survival.

Results: Compared with the 136 patients in the pCR group, the 113 patients in the WW group were older (median [range], 67.2 [32.1-90.9] vs 57.3 [25.0-87.9] years, P < .001) with cancers closer to the anal verge (median [range] height from anal verge, 5.5 [0.0-15.0] vs 7.0 [0.0-13.0] cm). All 22 local regrowths in the WW group were detected on routine surveillance and treated by salvage surgery (20 total mesorectal excisions plus 2 transanal excisions). Pelvic control after salvage surgery was maintained in 20 of 22 patients (91%). No pelvic recurrences occurred in the pCR group. Rectal preservation was achieved in 93 of 113 patients (82%) in the WW group (91 patients with no local regrowths plus 2 patients with local regrowths salvaged with transanal excision). At 5 years, overall survival was 73% (95% CI, 60%-89%) in the WW group and 94% (95% CI, 90%-99%) in the pCR group; disease-free survival was 75% (95% CI, 62%-90%) in the WW group and 92% (95% CI, 87%-98%) in the pCR group; and disease-specific survival was 90% (95% CI, 81%-99%) in the WW group and 98% (95% CI, 95%-100%) in the pCR group. A higher rate of distant metastasis was observed among patients in the WW group who had local regrowth vs those who did not have local regrowth (36% vs 1%, P < .001).

Conclusions And Relevance: A WW strategy for select rectal cancer patients who had a clinical complete response after neoadjuvant therapy resulted in excellent rectal preservation and pelvic tumor control; however, in the WW group, worse survival was noted along with a higher incidence of distant progression in patients with local regrowth vs those without local regrowth.
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http://dx.doi.org/10.1001/jamaoncol.2018.5896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459120PMC
April 2019

Positron-Emission Tomography Scan-Directed Chemoradiation for Esophageal Squamous Cell Carcinoma: No Benefit for a Change in Chemotherapy in Positron-Emission Tomography Nonresponders.

J Thorac Oncol 2019 03 1;14(3):540-546. Epub 2018 Nov 1.

Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Introduction: Preoperative or definitive chemoradiation is an accepted treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The MUNICON study showed that positron-emission tomography (PET) response following induction chemotherapy was predictive of outcomes in patients with gastroesophageal junction adenocarcinoma. We evaluated the predictive value of PET following induction chemotherapy in ESCC patients and assessed the impact of changing chemotherapy during radiation in PET nonresponders.

Methods: We retrospectively reviewed all patients with locally advanced ESCC who received induction chemotherapy and chemoradiation; all patients had a PET before and after induction chemotherapy. Survival was calculated from date of repeat PET using Kaplan-Meier analysis and compared between groups using the log-rank test.

Results: Of 111 patients, 70 (63%) were PET responders (defined as a 35% or more decrease in maximum standard uptake value) to induction chemotherapy. PET responders received the same chemotherapy during radiation. Of 41 PET nonresponders, 16 continued with the same chemotherapy and 25 were changed to alternative chemotherapy with radiation. Median progression-free survival (70.1 months versus 7.1 months, p < 0.01) and overall survival (84.8 months versus 17.2 months, p < 0.01) were improved for PET responders versus nonresponders. Median progression-free survival and overall survival for PET nonresponders who changed chemotherapy versus those who did not were 6.4 months versus 8.3 months (p = 0.556) and 14.1 versus 17.2 months (p = 0.81), respectively.

Conclusions: PET after induction chemotherapy highly predicts for outcomes in ESCC patients who receive chemoradiation. However, our results suggest that PET nonresponders do not benefit from changing chemotherapy during radiation. Future trials should use PET nonresponse after induction chemotherapy to identify poor prognosis patients for novel therapies.
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http://dx.doi.org/10.1016/j.jtho.2018.10.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640852PMC
March 2019

Outcomes of Radiation-Associated Esophageal Squamous Cell Carcinoma: The MSKCC Experience.

J Gastrointest Surg 2019 01 13;23(1):11-22. Epub 2018 Sep 13.

Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Objective: Esophageal squamous cell carcinoma (ESCC-R) is a rarely encountered sequela of chest radiation. Treatment is limited by toxicity with reirradiation and complex surgical dissection in a previously radiated field. The clinical presentation, prognosis, and treatment selection of ESCC-R remain undefined.

Methods: A retrospective review of patients with esophageal squamous cell carcinoma at a single institution between 2000 and 2017 was performed to identify patients with previous radiation therapy (≥ 5 years delay). Clinicopathologic characteristics, treatment, and outcomes of ESCC-R (n = 69) patients were compared to patients with primary esophageal squamous cell carcinoma (ESCC) (n = 827). Overall survival (OS) and cumulative incidence of recurrence (CIR) were compared using log-rank and Gray's tests, respectively.

Results: Median time from radiation to ESCC-R was 18.2 years. The majority of ESCC-R patients were female and presented with earlier disease and decreased behavioral risk factors. ESCC-R treated with surgery alone had worse OS than ESCC (5-year 15 vs 33%; p = 0.045). Patients with ESCC-R who received neoadjuvant treatment had higher risk of postoperative in-house mortality (16.7 vs 4.2%; p = 0.032). Patients with ESCC-R treated with surgery alone and definitive chemoradiation had higher recurrence risk than those with neoadjuvant + surgery (5-year recurrence 55 and 45 vs 15%; p = 0.101).

Conclusion: Neoadjuvant chemotherapy or chemoradiation should be used whenever possible for ESCC-R as it is associated with lower risk of recurrence. The improved survival benefits of aggressive treatment must be weighed against the higher associated postoperative risks.
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http://dx.doi.org/10.1007/s11605-018-3958-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572721PMC
January 2019

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

Adv Radiat Oncol 2018 Jul-Sep;3(3):391-398. Epub 2018 May 9.

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

Purpose: The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors.

Methods And Materials: Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n = 79). Receiving both treatments within 1 month was considered concurrent (n = 35; 44%), and any treatment up to 6 months apart was considered sequential (n = 44; 56%). The primary endpoint of this study was the rate of Grade ≥2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables.

Results: A total of 79 patients were identified, with lung cancer (n = 45) and melanoma (n = 15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ≥2 AEs included pneumonitis (n = 5; 6%), esophagitis (n = 6; 8%), and dermatitis (n = 8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ≥2 esophagitis ( = .04).

Conclusions: Overall, Grade ≥2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.
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http://dx.doi.org/10.1016/j.adro.2018.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128092PMC
May 2018