Dietary Counseling Interventions During Radiation Therapy: A Systematic Review of Feasibility, Safety, and Efficacy.

Radiotherapy is a common cancer treatment, and concurrent nutritional interventions can maintain nutritional status and improve clinical and supportive care outcomes. However, optimal nutritional interventions during radiotherapy are not firmly established. Herein, we assessed the feasibility, safety, and efficacy of dietary counseling interventions without oral nutrition supplements on health outcomes in adults receiving radiotherapy for cancer in a systematic review. Prospective clinical trials that implemented nutritional counseling interventions during radiotherapy were identified from four databases from inception through December 2023. Feasibility, safety, and efficacy were extracted from 32 articles that described 23 randomized and 4 non-randomized clinical trials. The interventions included individualized nutritional counseling (n = 14 articles), nutritional counseling plus exercise (n = 4), and nutritional counseling focused on increasing or reducing intake of specific nutrients (n = 9). Trials targeted head and neck (n = 12), pelvic cancers (n = 14), and/or breast (n = 5) cancers. Control groups had variable designs and included general nutrition education and intervention as needed. Studies recruited 120 ± 104 participants (range 26-468). Interventions tended to be feasible regarding retention and attendance at sessions, though feasibility metrics varied among different interventions. Most interventions were safe with no studies reporting adverse events attributable to dietary intervention. Individualized dietary counseling interventions tended to lead to between-group differences favoring the intervention group in regard to improved nutritional status, maintenance or attenuation of loss of body mass, improved quality of life, and reduced radiation-induced toxicities. Diets that encouraged/discouraged specific nutrients tended to recruit patients receiving radiation to the pelvic area and resulted in positive or neutral effects on gastrointestinal symptoms. In conclusion, nutritional interventions appear to be feasible, safe, and effective during radiotherapy for various symptom outcomes.

Adherence to Guideline-Concordant Care and Its Effect on Survival in Black Patients with Head and Neck Cancers: A SEER-Medicare Analysis.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), Black patients continue to have worse survival when compared with White patients. The cause of this disparity is multifaceted and cannot be explained by one etiology alone. To investigate this disparity, we used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine adherence to guideline-concordant care (GCC) as defined by the National Comprehensive Cancer Network. PATIENTS AND METHODS: In this retrospective study, Medicare beneficiaries diagnosed with nonmetastatic HNSCC as their first cancer between 1992 and 2011 and a random sample of Medicare controls matched to cases (2:1) diagnosed between 2004 and 2011 (n = 16,378), were included in this analysis. RESULTS: Black patients were less likely to receive GCC in advanced-stage oropharyngeal (66% vs. 74%; p = .007) and oral cavity (56% vs. 71%; p = .002) squamous cell carcinoma (SCC). On multivariate analysis, Black patients demonstrated an increased risk of death in advanced oropharyngeal (p < .001), oral cavity (p = .01), and hypopharyngeal (p = .01) SCC. CONCLUSION: Black patients did not consistently receive GCC across HNSCC subsites, contributing to the poorer outcomes seen when compared with White patients. Future research should focus on elucidating the mechanisms behind the non-GCC given to Black patients with HNSCC and other factors that may contribute to this disparity such as tumor biology. IMPLICATIONS FOR PRACTICE: Black patients with head and neck cancer (HNC) continue to have worse survival than White patients. This study examined if the racial disparity in survival from curable HNC is affected by adherence to guideline-concordant care (GCC). It was discovered that Black patients were less likely to receive appropriate treatment in certain HNCs. Although adherence to proper therapy was associated with improved survival in patients with HNC, the difference in survival, where Black patients had inferior outcomes, remained. This analysis uncovered a major contributor to the disparity seen in patients with HNC. As such, cancer centers serving a predominantly Black population with HNC can design specific clinical interventions to ensure GCC for all patients, potentially improving outcomes for everyone.

Neutrophil-Lymphocyte Ratio Is a Prognostic Marker in Patients with Locally Advanced (Stage IIIA and IIIB) Non-Small Cell Lung Cancer Treated with Combined Modality Therapy.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in localized and advanced non-small cell lung cancer (NSCLC). Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesized that low NLR at diagnosis is associated with improved overall survival (OS) in locally advanced NSCLC (LANSCLC) patients. PATIENTS AND METHODS: Records from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline demographic data and pretreatment peripheral blood absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used for multivariable analysis. RESULTS: The NLR was prognostic for OS (p < .0001). Median survival in months (95% confidence interval) for the first, second, third, and fourth quartile groups of the population distribution of NLR were 27 (19-36), 28 (22-34), 22 (12-31), and 10 (8-12), respectively. NLR remained prognostic for OS after adjusting for race, sex, stage, performance status, and chemoradiotherapy approach (p = .004). CONCLUSION: To our knowledge, our series is the largest to demonstrate that baseline NLR is a significant prognostic indicator in LANSCLC patients who received definitive chemoradiation with or without surgery. As an indicator of inflammatory response, it should be explored as a potential predictive marker in the context of immunotherapy and radiation therapy. IMPLICATIONS FOR PRACTICE: Neutrophil-lymphocyte ratio measured at the time of diagnosis was associated with improved overall survival in 276 patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) treated with definitive chemoradiation with or without surgery. To our knowledge, our series is the largest to demonstrate that baseline neutrophil-lymphocyte ratio is a significant prognostic indicator in locally advanced NSCLC patients who received definitive chemoradiation with or without surgery. Neutrophil-lymphocyte ratio is an inexpensive biomarker that may be easily utilized by clinicians at the time of locally advanced NSCLC diagnosis to help predict life expectancy.

Psychosocial Factors That Influence a Woman's Decision to Enroll in a Clinical Trial: Implications on How to Improve Clinical Trial Enrollment Among Black Women.

PURPOSE: Black women with breast cancer often present with more aggressive disease compared with other races, contributing to an increased risk of cancer mortality. Despite this inequity, Black women remain severely underrepresented in breast cancer clinical trials. We aim to characterize factors that influence a woman's decision to enroll in a clinical trial, with the goal of identifying clinical interventions to aid in the recruitment of vulnerable groups. METHODS AND MATERIALS: A cross-sectional, descriptive study was conducted using a questionnaire adapted from 2 prevalidated surveys investigating factors influencing clinical trial enrollment. The survey was administered to women with curable breast cancer during a single follow-up visit at 4 different sites within a university medical system where all patients are screened for clinical trial eligibility. Chi-square tests and Mann-Whitney U tests were used to assess associations or differences between the populations. RESULTS: One hundred ninety-four out of 209 women completed the survey, giving a compliance rate of 93%. Twenty-six percent of women self-identified as Black, most women were located at community sites (67.1%), most women had diagnoses of early-stage disease (I: 57.7%, II: 29.4%), and 81% of women had some collegiate-level education. Black women were younger at diagnosis (P = .005) and less likely to be married (P = .012) but more often lived with family members (P = .003) and had a lower median income (P < .001). According to the survey, Black women were less likely to trust their care team (P = .032), more likely to believe that research ultimately harms minorities (P < .001), and had a stronger belief in God's will determining illness and wellness (P < .001). Recurring themes of trust in the health care team, patient education, and advancement of cancer treatments were discussed in the focus groups. CONCLUSIONS: Failure to offer clinical trials and mistrust in research institutions may pose the greatest hindrances to the enrollment of Black women in clinical trials. Empowering women through education and fostering trustworthy relationships can encourage greater clinical trial participation.

The Effect of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients With Stage III Non-Small Cell Lung Cancer.

PURPOSE: Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. METHODS AND MATERIALS: This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. RESULTS: Thirty-two percent of patients resided in an FPA (n = 183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P = .001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P = .002), lower pre-CRT body mass index (BMI) (P = .026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P = .005) or after CRT (15.1 vs 28.1 months, P = .002), residing in an FPA resulted in an OS detriment. CONCLUSIONS: We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

Racial Analysis of Clinical and Biochemical Outcomes in Patients With Prostate Cancer Treated With Low-Dose-Rate Brachytherapy.

PURPOSE: Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa. METHODS: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure. RESULTS: One hundred and sixty-seven patients were included in the analysis (Black: n = 81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P = .011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = .114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P = .42). Overall survival was comparable between racial groups (P = .972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001). CONCLUSIONS: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes.

Identifying Psychosocial Needs of Patients With Cancer Undergoing Curative Radiation Therapy in an Inner-City Academic Center to Address Racial Disparities.

PURPOSE: There are little data quantifying the psychosocial needs of patients with cancer undergoing definitive radiation therapy. These needs significantly affect patients' access to care and treatment outcomes. Thus, our study aimed to characterize the socioeconomic needs of patients with cancer treated at an academic institution in urban and suburban radiation clinics. METHODS AND MATERIALS: A prospective, cross-sectional analysis was performed of patients undergoing curative radiation therapy for head and neck, lung/thoracic, gynecologic, or gastrointestinal malignancies using a questionnaire consolidated from prevalidated surveys. Main outcomes were differences in psychosocial needs stratified by race (Black vs non-Black) and time point (pretreatment, 1 month, 6 months, and 1 year after completion of radiation treatment). χ2 and Mann-Whitney U testing determined statistical differences between selected variables. Binary logistic regression analysis identified predictors of certain socioeconomic needs. RESULTS: Two hundred twenty-one of 266 patients completed the survey, giving a compliance rate of 83%. Black patients were more likely to be single (79% vs 37%; P < .001), reside in zip codes with a lower median income (74% vs 42%; P < .001), and be seen at our inner-city photon location (60% vs 25%; P < .001) compared with non-Black patients. Significantly higher proportions of Black compared with non-Black patients had unmet needs regarding pain (67% vs 39%; P = .005), stress management (64.7% vs 43.3%; P = .009), transportation (64% vs 19%; P < .001), and smoking cessation (35% vs 8.7%; P < .001) when all time points were considered. On multivariate analysis, Black patients were 2.6, 2.2, 7.2, and 3.4 times more likely than non-Black patients to request assistance with pain, stress, transportation, and financial aid, respectively. CONCLUSIONS: We identified disparate psychosocial needs of our cancer population, where Black patients had greater unmet needs than non-Black patients. By doing so, we plan to develop pragmatic, targeted interventions that, when combined with guideline-concordant cancer care, can lead to improvements in cancer outcomes and quality of life before, during, and after radiation therapy.

Nutrition in Cancer: Evidence and Equality.

PURPOSE: Poor nutrition is highly implicated in the pathogenesis of cancer and affects the survival of patients during and after completion of definitive therapies. Mechanistic evidence accumulated over the last century now firmly places dysregulated cellular energetics within the emerging hallmarks of cancer. Nutritional intervention studies often aim to either enhance treatment effect or treat nutritional deficiencies that portend poor prognoses. Patients living within food priority areas have a high risk of nutritional need and are more likely to develop comorbidities, including diabetes, hypertension, renal disease, and cardiovascular risk factors. Unfortunately, there is currently a paucity of data analyzing the impact of food priority areas on cancer outcomes. METHODS: Therefore, we performed a review of the literature focusing on the molecular and clinical interplay of cancer and nutrition, the importance of clinical trials in elucidating how to intervene in this setting and the significance of including citizens who live in food priority areas in these future prospective studies. CONCLUSIONS: Given the importance of nutrition as an emerging hallmark of cancer, further research must be aimed at directing the optimal nutrition strategy throughout oncologic treatments, including the supplementation of nutritious foods to those that are otherwise unable to attain them.

Insurance Status is an Independent Predictor of Overall Survival in Patients With Stage III Non-small-cell Lung Cancer Treated With Curative Intent.

INTRODUCTION: Population studies suggest an impact of insurance status on oncologic outcomes. We sought to explore this in a large single-institution cohort of patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analyzed 342 consecutive patients (January 2000 to December 2013) curatively treated for stage III NSCLC. Patients were categorized by insurance status as uninsured (U), Medicare/Medicaid + Veterans Affairs (M/M + VA), or Private (P). The χ2 test was utilized to compare categorical variables. The Kaplan-Meier approach and the Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR). RESULTS: Compared with M/M + VA patients, P insurance patients were more likely to be younger (P < .001), married (P < .001), Caucasian (P = .001), reside in higher median income zip codes (P < .001), have higher performance status (P < .001), and undergo consolidation chemotherapy (P < .001) and trimodality therapy (P < .001). Diagnosis to treatment was delayed > 30 days in U (67.3%), M/M + VA (68.1%), and P (52.6%) patients (P = .017). Compared with the M/M + VA and U cohorts, P insurance patients had improved OS (median/5-year: 30.7 months/34.2%, 19 months/17%, and 16.9 months/3.8%; P < .001) and FFR (median/5-year: 18.4 months/27.3%, 15.2 months/23.2%, and 11.4 months/4.8%; P = .012), respectively. On multivariate analysis, insurance status was an independent predictor for OS (P = .017) but not FFR. CONCLUSION: Compared with U or M/M + VA patients, P insurance patients with stage III NSCLC were more likely to be optimally diagnosed and treated, resulting in a doubling of median OS for P versus U patients. Improved access to affordable health insurance is critical to combat inequities in access to care and has potential for improvements in cancer outcomes.

Techniques for Treating Bilateral Breast Cancer Patients Using Pencil Beam Scanning Technology.

PURPOSE: Patients with bilateral breast cancer (BBC), who require postmastectomy radiation therapy or radiation as part of breast conservation treatment, present a unique technical challenge. Even with modern techniques, such as intensity modulated radiation therapy or volumetric modulated arc therapy (VMAT), adequate target coverage is rarely achieved without the expense of increased integral dose to important organs at risk (OARs), such as the heart and lungs. Therefore, we present several BBC techniques and a treatment algorithm using intensity-modulated proton therapy (IMPT) for patients treated at our center. MATERIALS AND METHODS: We describe 3 different BBC treatment techniques using IMPT on patients treated at our center, with comparison VMAT plans to demonstrate the dosimetric benefit of proton therapy in these patients. Following RADCOMP (Radiation Therapy Oncology Group, Philadelphia, Pennsylvania) guidelines, a single physician approved all target volumes and OARs. Plans were designed so that ≥ 95% of the prescribed dose covered ≥ 95% of all targets. Parameters for dosimetric volume histograms for the clinical targets and OARs are reported for the 2 radiation methods. RESULTS: All methods demonstrated acceptable target coverage with 95% of the prescription planning target volume reaching a mean (± SD) of 98.0% (± 0.87%) and 97.5% (± 2.39%), for VMAT and IMPT plans, respectively. Conformity and homogeneity were also similar between the 2 techniques. Proton therapy provided observed improvements in mean heart dose (average heart mean [SD], 9.98 Gy [± 0.87 Gy] versus 2.12 Gy [± 0.96 Gy]) and total lung 5% prescription dose (V5; mean [SD] total lung V5, 97.9% [± 2.84%]), compared with 39.8% [± 9.39%]). All IMPT methods spared critical OARs; however, the single, 0° anterior-posterior plan allowed for the shortest treatment time. CONCLUSION: Both VMAT and all 3 IMPT techniques provided excellent target coverage in patients with BBC; however, proton therapy was superior in decreasing the dose to OARs. A single-field optimization approach should be the IMPT method of choice when feasible.

Preserving Endocrine Function in Premenopausal Women Undergoing Whole Pelvis Radiation for Cervical Cancer.

PURPOSE: Whole pelvis radiation therapy (WPRT) in premenopausal women with cervical cancer can cause permanent ovarian damage, resulting in premature menopause. Oophoropexy, often considered as an initial step, demonstrates safety of sparing 1 ovary at the cost of delay in initiating WPRT. Therefore, we dosimetrically compared volumetric modulated arc radiotherapy (VMAT) and intensity modulated proton therapy (IMPT) techniques to allow for ovarian-sparing WPRT. MATERIALS AND METHODS: Ten patients previously treated for cervical cancer at our institution were included in this institutional review board-approved analysis. A modified clinical treatment volume (CTV) was designed, sparing 1 ovary (left or right), as determined by the physician (ovarian-sparing CTV) and disease extent, including physical exam, positron emission tomography/computed tomography and magnetic resonance imaging. An ovarian-sparing planning target volume was determined as the ovarian-sparing CTV+5 mm for patients who were supine and 7 mm for those who were prone. All plans were calculated to a dose of 45 Gy with specific optimization goals for target volumes, while attempting to maintain a mean ovary dose (Dmean) < 15 Gy. Dosimetric goals were compared across the 2 modalities using the Mann-Whitney U test. RESULTS: Both treatment modalities were able to achieve primary clinical goal coverage to the uterus/cervix (P = .529, comparing VMAT versus IMPT), ovarian-sparing CTV (P = .796) and ovarian-sparing planning target volume (P = .004). All 10 IMPT plans were able to accomplish the ovary objective (14.0 ± 1.66 Gy). However, only 4 of the 10 VMAT plans were able to achieve a Dmean < 15 Gy to the prioritized ovary, with an average dose of 15.3 ± 4.10 Gy. CONCLUSION: Sparing an ovary in women undergoing WPRT for cervical cancer is dosimetrically feasible with IMPT without sacrificing coverage to important clinical targets. Future work will incorporate the brachytherapy dose to the ovarian-sparing CTV and assess the clinical response of this technique as a means to preserve ovarian endocrine function.

Patterns of Care and Survival in Stage III NSCLC Among Black and Latino Patients Compared With White Patients.

BACKGROUND: Race and socioeconomic status have continued to affect the survival and patterns of care of patients with non-small-cell lung cancer (NSCLC). However, data evaluating these associations in patients with stage III disease remain limited. Therefore, we investigated the patterns of care and overall survival (OS) of black and Latino patients with locally advanced NSCLC compared with white patients, using the National Cancer Database. MATERIALS AND METHODS: All patients with stage III NSCLC from 2004 to 2013 who had undergone external beam radiotherapy (RT) alone, RT with chemotherapy (bimodality), or RT with chemotherapy followed by surgery (trimodality) were analyzed within the National Cancer Database according to race (n = 113,945). Univariate associations among the demographic, disease, and treatment characteristics within the 3 cohorts were assessed using χ2 tests. The OS between cohorts were analyzed using the log-rank test and multivariate Cox proportional hazards regression. RESULTS: The black and Latino patients were younger at diagnosis, had lower median household incomes, and were less likely to be insured than were the white patients. The black patients were more likely to receive RT alone (19.3% vs. 18%; P < .001) and less likely to have undergone concurrent chemo-RT (53.6% vs. 56.1%; P < .001) compared with the white patients. Black patients had improved OS (P < .001). In contrast, the Latino patients had survival equivalent to that of the white patients (P = .920). CONCLUSIONS: Despite epidemiologic differences and a propensity for less aggressive treatment, black patients with locally advanced NSCLC had better OS than white patients and Latino patients had equivalent outcomes. Additional research is needed to elucidate this finding, perhaps focusing on biological differences among the cohorts.

Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non-small-cell Lung Cancer at Diagnosis.

BACKGROUND: We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non-small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases. MATERIALS AND METHODS: A retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed. RESULTS: The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009). CONCLUSION: Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.

Reirradiation for locoregionally recurrent non-small cell lung cancer.

Locoregional failure in non-small cell lung cancer (NSCLC) remains high, and the management for recurrent disease in the setting of prior radiotherapy is difficult. Retreatment options such as surgery or systemic therapy are typically limited or frequently result in suboptimal outcomes. Reirradiation (reRT) of thoracic malignancies may be an optimal strategy for providing definitive local control and offering a new chance of cure. Yet, retreatment with radiation therapy can be challenging for fear of excessive toxicities and the inability to safely deliver definitive (≥60 Gy) doses of reRT. However, with recent improvements in radiation delivery techniques and image-guidance, dose-escalation with reRT is possible and outcomes are encouraging. Here, we present a review of various radiation techniques, clinical outcomes and associated toxicities in patients with locoregionally recurrent NSCLC treated primarily with reRT.

Advances in proton therapy in lung cancer.

Lung cancer remains the leading cause of cancer deaths in the United States (US) and worldwide. Radiation therapy is a mainstay in the treatment of locally advanced non-small cell lung cancer (NSCLC) and serves as an excellent alternative for early stage patients who are medically inoperable or who decline surgery. Proton therapy has been shown to offer a significant dosimetric advantage in NSCLC patients over photon therapy, with a decrease in dose to vital organs at risk (OARs) including the heart, lungs and esophagus. This in turn, can lead to a decrease in acute and late toxicities in a population already predisposed to lung and cardiac injury. Here, we present a review on proton treatment techniques, studies, clinical outcomes and toxicities associated with treating both early stage and locally advanced NSCLC.

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer.

PURPOSE: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). METHODS AND MATERIALS: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. RESULTS: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P = .004; FFR: HR 0.426, 95% CI 0.250-0.726, P = .002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P = .001; FFR: HR 0.455, 95% CI 0.266-0.778, P = .004). However, pCR did not independently impact OS (P = .918) or FFR (P = .474). CONCLUSIONS: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

Clinical outcomes of black vs. non-black patients with locally advanced non-small cell lung cancer.

OBJECTIVES: The black population remains underrepresented in clinical trials despite reports suggesting greater incidence and deaths from locally advanced non-small cell lung cancer (NSCLC). We determined outcomes for black and non-black patients in a well-annotated cohort treated with either definitive chemoradiation (CRT; bimodality) or CRT followed by surgery (trimodality therapy). MATERIALS AND METHODS: A retrospective analysis of 355 stage III NSCLC patients treated with curative intent at the University of Maryland, Medical Center, between January 2000-December 2013 was performed. The Kaplan-Meier approach and the Cox proportional hazards models were used to analyze overall survival (OS) and freedom-from-recurrence (FFR) in black and non-black patients. The chi-square test was used to compare categorical variables. RESULTS: Black patients comprised 42% of the cohort and were more likely to be younger (p<0.0001), male (p=0.030), single (p<0.0001), reside in lower household income zipcodes (p<0.0001), have an Eastern Cooperative Oncology Group (ECOG) performance status >0 (p<0.001), and less likely to undergo surgery (p<0.0001). With a median follow-up of 15 months for all patients and 89 months for surviving patients (range:1-186 months), median OS times for black and non-black patients were 22 and 24 months, respectively (p=0.698). FFR rates were also comparable between the two groups (p=0.468). Surgery improved OS in both cohorts. Race was not a significant predictor for OS or FFR even when adjusted for other factors. CONCLUSIONS: We found similar oncologic outcomes in black and non-black NSCLC patients when treated with curative intent in a comprehensive cancer center setting, despite epidemiologic differences in presentation and receipt of care. Future efforts to improve outcomes in black patients could focus on addressing modifiable social disparities.

Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy) and factors influencing consideration for surgery in stage III non-small cell lung cancer.

PURPOSE: Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. METHODS AND MATERIALS: We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. RESULTS: Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. CONCLUSIONS: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.