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 KaplanMeier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR

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Abstract:The 21st century has seen several paradigm shifts in the treatment of non-small cell lung cancer (NSCLC) in early-stage inoperable disease, definitive locally advanced disease, and the postoperative setting.A key driver in improvement of local disease control has been the significant evolution of radiation therapy techniques in the last three decades, allowing for delivery of definitive radiation doses while limiting exposure of normal tissues. For patients with locally-advanced NSCLC, the advent of volumetric imaging techniques has allowed a shift from 2-dimensional approaches to 3-dimensional conformal radiation therapy (3DCRT).The next generation of 3DCRT, intensity-modulated radiation therapy and volumetric-modulated arc therapy (VMAT), have enabled even more conformal radiation delivery. Clinical evidence has shown that this can improve the quality of life for patients undergoing definitive management of lung cancer. In the earlystage setting, conventional fractionation led to poor outcomes. Evaluation of altered dose fractionation with the previously noted technology advances led to advent of stereotactic body radiation therapy (SBRT). This technique has dramatically improved local control and expanded treatment options for inoperable, earlystage patients. The recent development of proton therapy has opened new avenues for improving conformity and the therapeutic ratio. Evolution of newer proton therapy techniques, such as pencil-beam scanning (PBS), could improve tolerability and possibly allow reexamination of dose escalation. These new progresses, along with significant advances in systemic therapies, have improved survival for lung cancer patients across the spectrum of non-metastatic disease. They have also brought to light new challenges and avenues for further research and improvement.

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.

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.

PurposeGuidelines 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 materialsWe 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.ResultsPatients 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.ConclusionsTrimodality 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.

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

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.