Association of low adherence to weekly cisplatin with outcomes in patients with head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. METHODS: Our institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. RESULTS: Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8-65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58-5.47, p < 0.001) and progression-free survival (aHR 2.32, 95% CI 1.29-4.17, p = 0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19-17.3, p = 0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46-5.58, p = 0.46). KPS < 90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10-6.65, p = 0.03). CONCLUSION: Our study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.

Vertebral body collapse after spine stereotactic body radiation therapy: a single-center institutional experience.

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) for the treatment of metastatic disease is increasingly utilized owing to improved pain and local control over conventional regimens. Vertebral body collapse (VBC) is an important toxicity following spine SBRT. We investigated our institutional experience with spine SBRT as it relates to VBC and spinal instability neoplastic score (SINS). PATIENTS AND METHODS: Records of 83 patients with 100 spinal lesions treated with SBRT between 2007 and 2022 were reviewed. Clinical information was abstracted from the medical record. The primary endpoint was post-treatment VBC. Logistic univariate analysis was performed to identify clinical factors associated with VBC. RESULTS: Median dose and number of fractions used was 24 Gy and 3 fractions, respectively. There were 10 spine segments that developed VBC (10%) after spine SBRT. Median time to VBC was 2.4 months. Of the 11 spine segments that underwent kyphoplasty prior to SBRT, none developed subsequent VBC. No factors were associated with VBC on univariate analysis. CONCLUSIONS: The rate of vertebral body collapse following spine SBRT is low. Prophylactic kyphoplasty may provide protection against VBC and should be considered for patients at high risk for fracture.

Association of Insomnia and Obstructive Sleep Apnea with Worse Oral Mucositis and Quality of Life in Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND: Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL). METHODS: Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM. RESULTS: Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (p = 0.005), fatigue (p = 0.01), insomnia (p < 0.001), and sticky saliva (p = 0.002). Patients screening positive for OSA had worse physical function (p = 0.01), sticky saliva (p = 0.02), fatigue (p = 0.007), insomnia (p = 0.009), and pain (p = 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (p = 0.01) and positive OSA screen (p = 0.002) were associated with worse OM. CONCLUSION: Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.

Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management. OBJECTIVE: In this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence. METHODS: We conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only. RESULTS: Patients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy. CONCLUSION: This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

Sinoatrial Node Dose Is Associated With Worse Survival in Patients Undergoing Definitive Stereotactic Body Radiation Therapy for Central Lung Cancers.

PURPOSE: Our purpose was to evaluate the clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing stereotactic body radiation therapy (SBRT) for central non-small cell lung cancer (NSCLC) tumors. METHODS AND MATERIALS: A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located thoracic tumors from February 2007 to December 2021 was performed. The SAN and AVN were contoured in accordance with a published contouring atlas, and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and overall survival. RESULTS: Among 93 eligible patients, the median age was 72.5 years (IQR, 66.6-78.3), and median follow-up was 32.4 months (IQR, 13.0-49.6). The median SAN Dmax and Dmean were 95 cGy (range, 9-5394) and 58 cGy (range, 7-3168), respectively. The median AVN Dmax and Dmean were 45 cGy (range, 4-2121) and 34 cGy (range, 3-1667), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1309 and 836 cGy, respectively. No associations between AVN parameters and survival outcomes were identified. Upon multivariate Cox regression, the SAN Dmax cutoff (hazard ratio [HR], 2.03 [1.09-3.79]; P = .026) and SAN Dmean cutoff (HR, 2.22 [1.20-4.12]; P = .011) were significantly associated with overall survival. For noncancer-associated survival, the SAN Dmax cutoff trended toward significance (HR, 2.02 [0.89-4.57]; P = .092), and the SAN Dmean cutoff remained significantly associated (HR, 2.34 [1.05-5.18]; P = .037). CONCLUSIONS: For patients undergoing SBRT for NSCLC, SAN Dmax and Dmean were significantly associated with worse overall survival using cut-off values of 1309 and 836 cGy, respectively. Further studies examining the effect of SAN irradiation during SBRT are warranted.

Long-Term Survival and Failure Outcomes of Single-Fraction Stereotactic Body Radiation Therapy in Early Stage NSCLC.

Introduction: This study aims to report our 13-year institutional experience with single-fraction stereotactic body radiation therapy (SF-SBRT) for early stage NSCLC. Methods: A single-institutional retrospective review of patients with biopsy-proven peripheral cT1-2N0M0 NSCLC undergoing definitive SF-SBRT between September 2008 and May 2022 was performed. All patients were treated to 27 Gy with heterogeneity corrections or 30 Gy without. Primary outcomes were overall survival and progression-free survival. Secondary outcomes included local failure, nodal failure, distant failure, and second primary lung cancer. Results: Among 263 eligible patients, the median age was 76 years (interquartile range [IQR]: 70-81 y) and median follow-up time was 27.2 months (IQR: 14.25-44.9 mo). Median tumor size was 1.9 cm (IQR: 1.4-2.6 cm), and 224 (85%) tumors were T1. There were 92 patients (35%) alive at the time of analysis with a median follow-up of 34.0 months (IQR: 16.6-50.0 mo). Two- and five-year overall survival was 65% and 26%, respectively. A total of 74 patients (28%) developed disease progression. Rates of five-year local failure, nodal failure, distant failure, and second primary lung cancer were 12.7%, 14.7%, 23.5%, and 12.0%, respectively. Conclusions: Consistent with multiple prospective randomized trials, in a large real-world retrospective cohort, SF-SBRT for peripheral early stage NSCLC was an effective treatment approach.

Severe Oral Mucositis After Intensity-Modulated Radiation Therapy for Head and Neck Cancer.

Importance: Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice. Objective: To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life. Design, Setting, and Participants: This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023. Main Outcomes and Measures: Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes. Results: Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001). Conclusions and Relevance: In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.

Association of Body Mass Index With Outcomes Among Patients With Head and Neck Cancer Treated With Chemoradiotherapy.

Importance: Combined modality therapy, such as chemoradiotherapy, often results in significant morbidity among patients with head and neck cancer. Although the role of body mass index (BMI) varies based on cancer subtypes, its association with treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer remains unclear. Objective: To evaluate the role of BMI in treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer undergoing chemoradiotherapy. Design, Setting, and Participants: This retrospective, observational, single-institution cohort study conducted at a comprehensive cancer center included 445 patients with nonmetastatic head and neck cancer who underwent chemoradiotherapy from January 1, 2005, to January 31, 2021. Exposure: Normal vs overweight or obese BMI. Main Outcomes and Measures: Metabolic response after chemoradiotherapy, locoregional failure (LRF), distant failure (DF), overall survival (OS), and progression-free survival (PFS), with Bonferroni correction used to adjust for multiple comparisons and P < .025 being considered statistically significant. Results: A total of 445 patients (373 men [83.8%]; median age, 61 years [IQR, 55-66 years]; 107 [24.0%] with normal BMI, 179 [40.2%] with overweight BMI, and 159 [35.7%] with obese BMI) were included for analysis. Median follow-up was 48.1 months (IQR, 24.7-74.9 months). On Cox proportional hazards regression multivariable analysis, only overweight BMI was associated with improved OS (5-year OS, 71.5% vs 58.4%; adjusted hazard ratio [AHR], 0.59 [95% CI, 0.39-0.91]; P = .02) and PFS (5-year PFS, 68.3% vs 50.8%; AHR, 0.51 [95% CI, 0.34-0.75]; P < .001). On logistic multivariable analysis, overweight BMI (91.6% vs 73.8%; adjusted odds ratio [AOR], 0.86 [95% CI, 0.80-0.93]; P < .001) and obese BMI (90.6% vs 73.8%; AOR, 0.89 [95% CI, 0.81-0.96]; P = .005) were associated with complete metabolic response on follow-up positron emission tomography-computed tomography after treatments. On Fine-Gray multivariable analysis, overweight BMI was associated with reduction in LRF (5-year LRF, 7.0% vs 25.9%; AHR, 0.30 [95% CI, 0.12-0.71]; P = .01), but not DF (5-year DF, 17.4% vs 21.5%; AHR, 0.92 [95% CI, 0.47-1.77]; P = .79). Obese BMI was not associated with LRF (5-year LRF, 10.4% vs 25.9%; AHR, 0.63 [95% CI, 0.29-1.37]; P = .24) or DF (5-year DF, 15.0% vs 21.5%; AHR, 0.70 [95% CI, 0.35-1.38]; P = .30). Conclusion: In this cohort study of patients with head and neck cancer, when compared with normal BMI, overweight BMI was an independent factor favorably associated with complete response after treatments, OS, PFS, and LRF. Further investigations are warranted to improve understanding on the role of BMI among patients with head and neck cancer.

Association of pre-treatment lymphocyte-monocyte ratio with survival outcome in patients with head and neck cancer treated with chemoradiation.

BACKGROUND: Given the role of systematic inflammation in cancer progression, lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of LMR with survival outcomes in North American patients with head and neck cancer. METHODS: A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation from June 2007 to April 2021 at the Roswell Park Comprehensive Cancer Center. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS). Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze OS and CSS. Pre-radiation LMR was then stratified into high and low based on its median value. Propensity scored matching was used to reduce the selection bias. RESULTS: A total of 476 patients met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio [aHR] 0,90, 95% confidence interval [CI] 0.82-0.99, p = 0.03) and CSS (aHR 0.83, 95% CI 0.72-0.95, p = 0.009). The median value of LMR was 3.8. After propensity score matching, a total of 186 pairs were matched. Lower LMR than 3.8 remained to be associated with worse OS (HR 1.59, 95% CI 1.12-2.26, p = 0.009) and CSS (HR 1.68, 95% CI 1.08-2.63, p = 0.02). CONCLUSION: Low LMR, both as a continuous variable and dichotomized variable, was associated with worse OS and CSS. Further studies would be warranted to evaluate the role of such prognostic marker to tailor interventions.

Prophylactic High-Dose Gabapentin Reduces Opiate Use during Radiation Therapy for Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The role of prophylactic high-dose gabapentin for the management of oral mucositis during radiation therapy for head and neck squamous cell carcinoma (HNSCC) remains controversial. METHODS: A retrospective cohort analysis was performed on primary HNSCC patients treated at our institution. Kruskal-Wallis and Fisher's exact tests were used to compare the patients' baseline characteristics. Multivariate competing risk and logistic regressions were performed to evaluate time to first opioid use and feeding tube placement. RESULTS: In total, 480 consecutive HNSCC patients were included. Within this cohort, 186 patients received 3600 mg gabapentin, 182 received 300 to 3200 mg gabapentin, and 112 received no gabapentin. The time to first opioid use was greater in the 3600 mg group compared with the no gabapentin group (34.3 vs. 23.9 days, p < 0.001) and to the 300 to 3200 mg group (28.0 days, p < 0.001). The proportion of patients requiring opioids at any point during RT was lower in the 3600 mg gabapentin group compared with the no gabapentin group (31.8% vs. 60.1%, p < 0.001) and with the 300 to 3200 mg group (63.8%, p < 0.001). CONCLUSIONS: Prophylactic use of 3600 mg gabapentin was well tolerated, halved overall opioid use, and delayed the time to first opioid use during radiation therapy.

Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer.

BACKGROUND: Progesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear. METHODS: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively. RESULTS: Among 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23-17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10-1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47-0.67; PR-negative: aHR 0.31, 95% CI 0.20-0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66-0.82; PR-negative: aHR 0.63, 95% CI 0.51-0.77). CONCLUSION: PR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors.

Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy.

BACKGROUND: The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT. METHODS: A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. RESULTS: A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. CONCLUSIONS: Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.

Comparison of Survival Outcomes of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Early-Stage Central or Peripheral NSCLC.

BACKGROUND: The treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) frequently involves different fractionation schemes for peripheral and central tumors due to concerns with toxicity. We performed an observational cohort study to determine survival outcomes for patients with peripheral and central NSCLC treated with SBRT. METHODS: A single-institutional database of patients with early-stage NSCLC treated with SBRT from September 2008 to December 2018 was evaluated. Outcomes were progression-free survival (PFS), overall survival (OS), local failure (LF), nodal failure (NF), and distant failure (DF). Cox multivariable analysis (MVA), Kaplan-Meier plotting, Fine-Gray competing risk MVA, and propensity score matching were performed. RESULTS: A total of 265 patients were included with a median follow-up of 44.2 months. There were 191 (72%) and 74 (28%) patients with peripheral and central tumors treated with single-fraction SBRT to a dose of 27 Gy and five-fraction SBRT to a dose of 50 Gy, respectively. On Cox MVA, there was no difference in OS (adjusted hazards ratio (aHR) of 1.04, 95% CI of 0.74-1.46) or PFS (aHR of 1.05, 95% CI of 0.76-1.45). On Fine-Gray competing risk MVA, there were no differences in LF, NF, or DF. Propensity matching confirmed these findings. CONCLUSION: The survival outcomes of patients treated with SBRT for early-stage NSCLC were equivalent for central and peripheral tumors.

Efficacy of Prophylactic High-Dose Gabapentin and Venlafaxine on Reducing Oral Mucositis Pain Among Patients Treated With Chemoradiation for Head and Neck Cancer: A Single-Institution, Phase 2, Randomized Clinical Trial.

PURPOSE: Given the paucity of level 1 evidence, the optimal regimen to control oral mucositis pain remains unclear. Although national guidelines allow consideration of prophylactic gabapentin, prior trials showed improved pain control with venlafaxine among patients with diabetic neuropathy. We sought to investigate the role of prophylactic high-dose gabapentin with venlafaxine to reduce oral mucositis pain among patients with head and neck cancer. METHODS AND MATERIALS: We performed a single-institution, phase 2 randomized trial on nonmetastatic squamous cell carcinoma of the head and neck treated with chemoradiation. Patients were randomized to either prophylactic gabapentin (3600 mg daily) with or without venlafaxine (150 mg daily). Primary endpoint was differences in pain levels at the end of chemoradiation. Secondary endpoint was toxicity profiles, quality of life changes, opioid use, and feeding tube placement. Differences between the 2 arms at multiple time points were evaluated using a generalized linear mixed regression model with Sidak correction. RESULTS: Between May 2018 and March 2021, a total of 62 patients were enrolled and evaluable for analysis (n = 32 for the gabapentin alone arm, n = 30 for the gabapentin + venlafaxine arm). Over 90% of patients tolerated gabapentin well. Head and neck pain level showed a mean value of 45 (standard deviation, 23) and 43 (standard deviation, 21) for the gabapentin alone and the gabapentin + venlafaxine arms, respectively (P = .65). No statistically significant differences were observed in adverse events, opioid use, feeding tube placement, or quality of life. CONCLUSIONS: The addition of venlafaxine to prophylactic gabapentin did not result in improvements in pain control and quality of life among patients with head and neck cancer.

Association of Neighborhood-Level Household Income With 21-Gene Recurrence Score and Survival Among Patients With Estrogen Receptor-Positive Breast Cancer.

Importance: While low income has been associated with a higher incidence of triple-negative breast cancer, its association with 21-gene recurrence score (RS) among patients with estrogen receptor (ER)-positive breast cancer remains unclear. Objective: To evaluate the association of household income with RS and overall survival (OS) among patients with ER-positive breast cancer. Design, Setting, and Participants: This cohort study used data from the National Cancer Database. Eligible participants included women diagnosed between 2010 and 2018 with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with or without chemotherapy. Data analysis was performed from July 2022 to September 2022. Exposures: Low vs high neighborhood-level household income levels defined as below vs above the median household income of $50 353 based on each patient's zip code. Main Outcomes and Measures: RS (a score ranged from 0 to 100 based on gene expression signatures indicating the risk of distant metastasis, with RS of 25 or below indicating non-high risk and RS above 25 indicating high risk) and OS. Results: Among 119 478 women (median [IQR] age, 60 [52-67] years; 4737 [4.0%] Asian and Pacific Islander, 9226 [7.7%] Black, 7245 [6.1%] Hispanic, 98 270 [82.2%] non-Hispanic White), 82 198 (68.8%) and 37 280 (31.2%) patients had high and low income, respectively. Logistic multivariable analysis (MVA) showed that, compared with high income, low income was associated with higher RS (adjusted odds ratio [aOR], 1.11; 95% CI, 1.06-1.16). Cox MVA showed that low income was also associated with worse OS (adjusted hazards ratio [aHR], 1.18; 95% CI, 1.11-1.25). Interaction term analysis showed a statistically significant interaction between income levels and RS (interaction P < .001). On subgroup analysis, significant findings were noted among those with RS below 26 (aHR, 1.21; 95% CI, 1.13-1.29), while there was no significant OS difference between income levels among others with RS of 26 or higher (aHR, 1.08; 95% CI, 0.96-1.22). Conclusions and Relevance: Our study suggested that low household income was independently associated with higher 21-gene recurrence scores and significantly worse survival outcomes among those with scores below 26, but not 26 or higher. Further studies are warranted to investigate the association between socioeconomic determinants of health and intrinsic tumor biology among patients with breast cancer.

Brachial Plexopathy After Single-Fraction Stereotactic Body Radiation Therapy in Apical Lung Tumors.

PURPOSE: The objective of this study was to evaluate the incidence of brachial plexus injury (BPI) after single-fraction stereotactic body radiation therapy (SBRT) to apical lung tumors. METHODS AND MATERIALS: A retrospective cohort analysis was performed of all patients treated with single-fraction lung SBRT at our institution from 2007 to 2022. Apical tumors were identified as those with an epicenter located above the arch of the aorta. Dosimetric analysis of dose to the brachial plexus (BP) was done using both the subclavian vessel (SCV) surrogate structure and anatomic BP. BPI was assessed per Common Terminology Criteria for Adverse Events, version 4.0, as regional paresthesia, marked discomfort and muscle weakness, and limited movement of the arm or hand. RESULTS: A total of 45 patients met inclusion criteria with median follow-up of 21 months. There were 9 patients who exceeded the BP dose constraint using the SCV or anatomic BP volume. Only 1 patient (2.2%) developed grade 2 BPI, occurring 7 months after SBRT. Dose to the anatomic BP for the affected patient was 26.39 Gy. For the entire cohort, the median SCV and anatomic maximum BP doses were 8.44 and 7.14 Gy, respectively. CONCLUSIONS: There is considerable variability in dose delivered to the BP after SBRT to apical lung tumors. BPI after single-fraction SBRT to apical tumors is rare and rates are comparable with those reported with multifraction regimens.

Association of Pack-Years of Cigarette Smoking With Survival and Tumor Progression Among Patients Treated With Chemoradiation for Head and Neck Cancer.

Importance: After 10 pack-years of smoking was initially established as a threshold for risk stratification, subsequent clinical trials incorporated it to identify candidates for treatment deintensification. However, several recent studies were unable to validate this threshold externally, and the threshold for smoking exposure remains unclear. Objective: To estimate the threshold of pack-years of smoking associated with survival and tumor recurrence among patients with head and neck cancer. Design, Setting, and Participants: This single-institution, cohort study included patients with nonmetastatic head and neck cancer receiving chemoradiation from January 2005 to April 2021. Data were analyzed from January to April 2022. Exposures: Heavy vs light smoking using 22 pack-years as a threshold based on maximizing log-rank test statistic. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), locoregional failure (LRF), and distant failure (DF). Results: A total of 518 patients (427 male [82.4%]; median [IQR] age, 61 [55-66] years) were included. Median (IQR) follow-up was 44.1 (22.3-72.8) months. A nonlinear Cox regression model using restricted cubic splines showed continuous worsening of OS and PFS outcomes as pack-years of smoking increased. The threshold of pack-years to estimate OS and PFS was 22. Cox multivariable analysis (MVA) showed that more than 22 pack-years was associated with worse OS (adjusted hazard ratio [aHR] 1.57; 95% CI, 1.11-2.22; P = .01) and PFS (aHR, 1.38; 95% CI, 1.00-1.89; P = .048). On Fine-Gray MVA, heavy smokers were associated with DF (aHR, 1.71; 95% CI, 1.02-2.88; P = .04), but not LRF (aHR, 1.07; 95% CI, 0.61-1.87; P = .82). When 10 pack-years of smoking were used as a threshold, there was no association for OS (aHR, 1.23; 95% CI, 0.83-1.81; P = .30), PFS (aHR, 1.11; 95% CI, 0.78-1.57; P = .56), LRF (aHR, 1.19; 95% CI, 0.64-2.21; P = .58), and DF (aHR, 1.45; 95% CI, 0.82-2.56; P = .20). Current smoking was associated with worse OS and PFS only among human papillomavirus (HPV)-positive tumors (OS: aHR, 2.81; 95% CI, 1.26-6.29; P = .01; PFS: aHR, 2.51; 95% CI, 1.22-5.14; P = .01). Conclusions and Relevance: In this cohort study of patients treated with definitive chemoradiation, 22 pack-years of smoking was associated with survival and distant metastasis outcomes. Current smoking status was associated with adverse outcomes only among patients with HPV-associated head and neck cancer.

Quality of Life After Stereotactic Body Radiation Therapy or Surgery for Early-Stage NSCLC: A Systematic Review.

Quality of life (QOL) is a key consideration for patients with early-stage NSCLC choosing between treatment options. Currently, it is not well established whether stereotactic body radiation therapy (SBRT) or surgery offers superior QOL in early-stage NSCLC. The objective of this systematic review is to summarize the prospective literature on QOL in patients with early-stage NSCLC after treatment with SBRT or surgery. A comprehensive literature review using PubMed and EMBASE was performed in April 2022. Prospective studies evaluating QOL data across multiple time points in patients with early-stage NSCLC after SBRT or surgery were included. A total of 25 studies involving 1597 SBRT patients and 1652 surgery patients met the inclusion criteria. Across most studies, QOL remained stable after treatment with SBRT. After surgery, QOL initially decreased; however, it often returned to baseline in the next 6 to 12 months. Utilization of video-assisted thoracoscopic surgery and sublobar resection reduced the magnitude of the initial decrease in QOL after surgery and led to faster recovery to baseline. Owing to the heterogeneity of patient populations between studies evaluating SBRT versus surgery, direct comparisons between the two treatments remain difficult to make. Clinicians should appropriately counsel patients with this information to help guide patient-centered discussions on choosing the optimal treatment modality.

Trends in Postoperative Intensity-Modulated Radiation Therapy Use and Its Association With Survival Among Patients With Incompletely Resected Non-Small Cell Lung Cancer.

Importance: National guidelines allow consideration of postoperative radiation therapy (PORT) among patients with incompletely resected non-small cell lung cancer (NSCLC). However, there is a paucity of prospective data because recently completed trials excluded patients with positive surgical margins. In addition, unlike for locally advanced NSCLC, the role of intensity-modulated radiation therapy (IMRT) for PORT remains unclear. Objective: To evaluate trends of IMRT use for PORT in the US and the association of IMRT with survival outcomes among patients with incompletely resected NSCLC. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database for patients diagnosed between January 2004 and December 2019 with incompletely resected NSCLC who underwent upfront surgery with positive surgical margins followed by PORT. Exposures: IMRT vs 3D conformal radiation therapy (3DCRT) for PORT. Main Outcomes and Measures: The main outcome was overall survival. Multivariable Cox proportional hazards regression assessed the association of IMRT vs 3DCRT with overall survival. Multivariable logistic regression identified variables associated with IMRT. Propensity score matching (1:1) was performed based on variables of interest. Results: A total of 4483 patients (2439 men [54.4%]; median age, 67 years [IQR, 60-73 years]) were included in the analysis. Of those, 2116 (47.2%) underwent 3DCRT and 2367 (52.8%) underwent IMRT. Median follow-up was 48.5 months (IQR, 31.1-77.2 months). The proportion of patients who underwent IMRT increased from 14.3% (13 of 91 patients) in 2004 to 70.7% (33 of 471 patients) in 2019 (P < .001). IMRT was associated with improved overall survival compared with 3DCRT (adjusted hazard ratio, 0.84; 95% CI, 0.78-0.91; P < .001). Similar findings were observed for 1463 propensity score-matched pairs; IMRT was associated with improved 5-year overall survival compared with 3DCRT (37.3% vs 32.2%; hazard ratio, 0.88; 95% CI, 0.80-0.96; P = .003). IMRT use was associated with receipt of treatment at an academic facility (adjusted odds ratio [aOR], 1.15; 95% CI, 1.00-1.33; P = .049), having T4 stage tumors (aOR, 1.50; 95% CI, 1.13-1.99; P = .005) or N2 or N3 stage tumors (aOR, 1.25; 95% CI, 1.04-1.51; P = .02), and receipt of pneumonectomy (aOR, 1.35; 95% CI, 1.02-1.80; P = .04). Conclusion and Relevance: This cohort study found that use of IMRT for PORT among patients with incompletely resected NSCLC increased in the US from 2004 to 2019 and was associated with improved survival compared with 3DCRT. Further studies are warranted to investigate the role of different radiation therapy techniques for PORT.