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Purpose: To investigate the feasibility of a 4D Monte Carlo based dose reconstruction method to study the dosimetric impact of respiratory motion using surface motion measurements for patients undergoing VMAT treatments for Non-Small Cell Lung Cancer., Methods: The 4Ddefdosxyznrc/EGSnrc algorithm was used to reconstruct VMAT doses delivered to the patients using machine log files and respiratory traces measured with the RADPOS 4D dosimetry system. The RADPOS sensor was adhered to the patient's abdomen prior to each treatment fraction and its position was used as a surrogate for tumour motion. Treatment log files were synchronized with the patient respiratory traces. Patient specific respiratory models were generated from deformable registration of the inhale and exhale 4DCT images and the respiratory traces. The reconstructed doses were compared to planned doses calculated with DOSXYZnrc/EGSnrc on the average-intensity and the exhale phase CT images., Results: Respiratory motion measurements and log files were acquired for 2 patients over 5 treatment fractions each. The motion was predominantly along the anterior/posterior direction (A/P). The average respiratory amplitudes were 8.7 ± 2.7 mm and 10.0 ± 1.2 mm for Patient 1 and 2, respectively. Both patients displayed inter- and intra-fractional variations in the baseline position. Small inter-fractional differences were observed in the reconstructed doses for each patient. Differences between the reconstructed and planned doses were attributed to differences in organ volumes., Conclusion: The 4D reconstruction method was successfully implemented for the two patients studied. Small differences between the planned and reconstructed doses were observed due to the small tumour motion of these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: To assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10 -2 with overall and failure-free survival of patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT)., Methods: A retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10 -2 ) from our previous data was used to group patients into low and high SGR cohorts. Log-rank test was used to compare overall (OS) and failure-free survivals (FFS) of SGR groups., Results: The median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P < 0.05), male gender (P = <0.01), and GTV2 (P = <0.05) were associated with poorer FFS., Conclusions: High SGR was associated with poorer outcome in patients with early-stage NSCLC treated with SBRT. SGR can be used in conjunction with other well-known predictive factors to formulate a practical predictive model to identify subgroups of the patient at higher risk of recurrence after SBRT., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment., Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions., Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified., Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: SAL has received honoraria from Pfizer, AstraZeneca, Boehringer Ingelheim, and Novartis; SB has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Eli Lilly, Novartis, Pfizer, and Roche, and has received research funding from AstraZeneca and Merck; NB has served on advisory boards for Amgen, AstraZeneca, Merck, Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, Celgene, Eli Lilly, Novartis, Pfizer, Sanofi, and Roche; SB has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Eisai, and Merck; PKC has served as an advisor for AstraZeneca, Boehringer Ingelheim, Hoffmann–La Roche, Pfizer, Novartis, Takeda, Eli Lilly, and Bristol–Myers Squibb, and has received research funding from Boehringer Ingelheim and Hoffmann–La Roche; PC has received grants for investigator-initiated research projects from AbbVie, Pfizer, and Sanofi–Aventis; DH has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, and Merck, and has received honoraria from Pfizer; VH has participated on advisory boards for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Merck, Pfizer, and Roche; RJ has served as an advisor or consultant for AstraZeneca/MedImmune, Bristol–Myers Squibb, Merck, Pfizer/emd Serono, and Roche, has received honoraria from AstraZeneca, Bristol–Myers Squibb, Merck, Pfizer/emd Serono, and Roche, and has received research funding from AstraZeneca, Bristol–Myers Squibb, and Merck; JL has received honoraria for talks from AstraZeneca, Boehringer Ingelheim, Pfizer, and Roche, and her institution has received grant funding for research trials from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Roche; in the last 2 years, NL has received honoraria for independent unrelated continuing medical education from AstraZeneca, Bristol–Myers Squibb, and Merck; DR has received honoraria and support from Accuray, BrainLab, Elekta, Pfizer/emd Serono, Siemens Healthineers, and Varian Medical Systems; JR has received speaker and advisory board fees and institutional research support for clinical trials funded by Astra-Zeneca, Bristol–Myers Squibb, Merck, Pfizer, and Roche; DJS has received honoraria (2015–2018) from Roche Canada, Boehringer Ingelheim Canada, Novartis Canada, Merck Canada, AstraZeneca Canada, Bristol–Myers Squibb Canada, Exactis Innovation, and Pfizer Canada, and has received institutional research support from Boehringer Ingelheim, AstraZeneca, Novartis, Bristol– Myers Squibb, and Celgene; MST has received honoraria from AstraZeneca, Bristol–Myers Squibb, Merck, and Roche/Ventana, and a research grant from Merck. The remaining authors have no conflicts to disclose.

Background: Many patients diagnosed with stage IIIB (AJCC sixth edition; T4, N3, or both; no pleural effusion) non-small-cell lung cancer (NSCLC) are treated with curative intent, despite a low cure rate. Guidelines are required to help select patients for radical therapy so that the patients with little chance of cure may be spared the toxicities of aggressive treatment. A retrospective analysis was performed to investigate factors influencing outcomes in these patients., Materials and Methods: From 2002 to 2009, all cases of stage IIIB NSCLC from the authors' institution were identified. Patients treated with radical radiotherapy (minimum dose, 50 Gy), with or without chemotherapy, were included. Charts were reviewed for patient demographic data, baseline blood work, tumor factors, treatment factors, and hospitalizations. The primary outcome was overall survival (OS), measured from time of diagnosis., Results: Of 238 patients identified, 184 eligible cases were reviewed. The median follow-up for all patients was 17.2 months (range, 1.7-237.1). The median progression-free survival was 10.8 months (95% CI, 9.6-12.4). Median survival was 17.9 months, and OS was 68%, 42%, and 28% at 1, 2, and 3 years, respectively. In multivariate analysis, female gender (hazard ratio [HR], 0.58; 95% CI, 0.37-0.88; P = .0013), ≤ 5% weight loss (HR, 0.64; 95% CI, 0.43-0.93; P = .01), and absence of N3 disease (HR, 0.64; 95% CI, 0.42-0.96; P = .03) were associated with significantly longer survival., Conclusion: OS was significantly longer in women, in patients with ≤ 5% weight loss, and in those without N3 disease. Good patient selection remains important in the radical treatment of stage IIIB NSCLC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [(18)F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT)., Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed., Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax <7 was better than that of the patients with tumor SUVmax ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival., Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Even if non-small-cell lung cancer (NSCLC) is diagnosed early and resected, recurrence is common. Uncertainty exists about the optimal treatment of locoregional recurrence. In fit patients with locoregional recurrence, chemoradiotherapy is sometimes offered, but no data exist about the feasibility and efficacy of this approach. We retrospectively collected data from patients treated this way to assess their outcomes and to identify prognostic factors., Patients and Methods: Databases of The Ottawa Hospital Cancer Centre (TOHCC) (N = 5791) and the Princess Margaret Hospital (PMH) (N = 2225) were screened to identify patients with recurrent NSCLC after curative resection who were offered curative-intent chemoradiotherapy. Selected patients' charts were reviewed., Results: Thirty patients fit our search criteria. The median disease-free interval was 15 months (2-33 months) and stage at recurrence was mainly T0 (n = 25 [83%]), N2 (n = 25 [83%]), and M0 (n = 29 [97%]). The median radiation dose given at recurrence was 63.5 Gy (26-66 Gy). Chemotherapy included a platinum agent in all cases, mostly a platinum-vinorelbine doublet (n = 14 [47%]), at a median of 3 cycles, (1-6 cycles) 2 of which were concurrent (0-3 cycles). Toxicities were as expected from thoracic chemoradiotherapy, with 7 cases of grade 4 toxicities and no treatment-related deaths. Median follow-up was 22 months (1.5-88 months). Median survival after recurrence was 26.9 months. No prognostic factors were identified., Conclusion: Chemoradiotherapy for locoregional recurrent NSCLC is practiced sporadically. This treatment is feasible for highly selected patients, and in our cohort, it allowed for a significantly higher than expected survival. No prognostic factors were identified. Chemoradiotherapy for locoregional NSCLC should be examined in a prospective trial., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: A new 4D in vivo dosimetry tool, RADPOS, has been used on lung cancer patients to evaluate the feasibility of using the detectors to characterize variations in patient breathing patterns as well as to monitor daily variations in dose., Methods and Materials: The RADPOS system combines a MOSFET dosimeter with an electromagnetic positioning sensor for simultaneous measurement of real-time dose and spatial coordinates. Three RADPOS sensors were placed on patients' chest and abdomen during a 4DCT and daily treatments. A fourth detector was also placed on the couch as reference. Position data were collected in real-time and total dose was read at the end of each fraction., Results: Significant deviations in surface motion have been found between the day of 4DCT and treatment fractions in 9 of 10 patients. Variations in daily dose ranged from 2.5 to 13.7 cGy (2.8-14.0%) and results agreed with treatment plan values for all but three points., Conclusions: Changes in breathing motion have been found that emphasize a need for continued position monitoring. RADPOS measurements can be used to monitor such variations as well as to measure surface dose without any disruption to the treatment schedule or discomfort to patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC)., Methods and Materials: Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy., Results: Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%., Conclusions: Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Anemia during chemoradiation is associated with poorer outcomes in various cancers. Concurrent chemoradiation (CCRT) is standard therapy for fit patients with limited small-cell lung cancer (LD-SCLC). The objective of this study was to explore the relationship between anemia and treatment outcomes in patients with LD-SCLC treated with CCRT., Methods: Charts of all patients with LD-SCLC receiving CCRT at The Ottawa Hospital Regional Cancer Centre between January 1996 and December 2002 were reviewed. Information extracted included demographics, known prognostic factors, treatment details, and hemoglobin values from diagnosis until the completion of therapy. Factors associated with outcomes were determined by Cox regression analyses., Results: One hundred thirty patients were eligible for inclusion, and their median survival was 18.1 months (95% CI, 14.8-25.1 months). By univariate analysis, poorer outcome was associated with Eastern Cooperative Oncology Group performance status > or =2, supraclavicular adenopathy, and pre-radiotherapy hemoglobin <100 g/liter. Pre-radiotherapy hemoglobin <100 g/liter was associated with both an increased risk of progression (hazard ratio 1.8; P = 0.04) and death (hazard ratio 1.9; P = 0.02) by multivariate analysis., Conclusion: Anemia during CCRT for LD-SCLC is common and may be associated with poorer outcome. Whether this association is causative or simply prognostic is unclear, and it is not known whether correction or prevention of anemia will improve outcome. Clinical trials evaluating different target hemoglobin levels and the roles of transfusion or erythropoietin during CCRT are needed.

Inconsistencies in the treatment planning process leading to dosimetric uncertainties may affect conclusions drawn from interinstitutional radiation oncology clinical trials. The purpose of this study was to assess the dosimetric uncertainties resulting from the process of reconstructing three-dimensional dose distributions from two-dimensional treatment plan information provided by participating institutions in a randomized clinical trial. This study was based on American College of Radiology Protocol #427, Locally Advanced Multi-Modality Protocol; a multi-institutional phase II randomized study involving radiation therapy for patients with inoperable non-small cell lung cancer. Several sources of dosimetric uncertainty were identified and analyzed, including image quality of hard-copy computed tomography (CT) images, slice spacing of CT scans, treatment position, interpretations of target volumes by radiation oncologists, the contouring of normal anatomic structures, and the use of common beam models for all dose calculations. Each source of uncertainty was investigated using a set of plans, with the ideal characteristics of digital images with 3-mm axial slice spacing and a flat couch, consisting of eight cases from Vanderbilt University Medical Center with electronically transferred CT data. The target volume DVH values were dependent on the additional uncertainty introduced by differences in delineation of the target volumes by the participating radiation oncologists. The DVH values for the lungs and heart were dependent on image quality and treatment position. Esophagus DVH values were not dependent on any of the sources of uncertainty. None of the structure DVH values were dependent on slice thickness or variations in the contouring of normal anatomic structures. Reconstruction of three-dimensional dose distributions from two-dimensional treatment plan information may be useful in cases for which digital CT data is not available or for historical data review. However, dosimetric accuracy will depend on image quality of the treatment planning CT data and consistency in the delineation of tumor volumes.

Chemoradiotherapy has become the standard treatment for patients with locally advanced non-small-cell lung cancer on the basis of several large randomized trials. Despite an increase in median survival from 10 months with radiotherapy alone to 16 to 17 months with concurrent chemoradiotherapy, long-term survival in this disease remains modest at best. With the advent of new biologic agents targeting specific cellular pathways associated with malignant progression, combined-modality therapy has the potential to target tumors selectively with less toxicity.

Background and Purpose: Tumor hypoxia and anemia have been linked to poor overall survival and local control in carcinomas of both the uterine cervix and the head and neck for patients undergoing radiotherapy. Little is known about the effect of these factors on the outcome of NSCLC patients with locally advanced disease undergoing chemoradiation therapy., Materials and Methods: To examine the impact of anemia in stage III NSCLC patients undergoing combined modality therapy, we reviewed our database from three sequential trials of concurrent weekly paclitaxel +/- carboplatin and radiation therapy. 115 pts from 17 institutions were enrolled from 4/94 to 5/97. In this series, hemoglobin values were collected before treatment and weekly during radiotherapy. We correlated baseline Hb and Hb changes during chemoradiation treatment with overall survival., Results: Although pretreatment anemia was common (30% Hb = 110-130 g/l, 16% Hb <110 g/l), log-rank analyses of presenting Hb, average Hb and minimum Hb during treatment were not statistically significantly predictive of survival. However in a Cox model, declining hemoglobin during chemoradiation had a statistically significant impact on survival., Conclusions: These analyses reveal that a decline in hemoglobin during chemoradiation for stage III NSCLC has a statistically significant correlation with overall survival. Strategies maximizing hemoglobin during combined modality therapy need further exploration in well-planned randomized trials., (Copyright 2002 Published by Elsevier Science Ireland Ltd.)

The results of randomized trials have prompted an evolution in the treatment approach to inoperable locally advanced non-small cell lung cancer, from radiotherapy alone to sequential chemoradiotherapy and now to concurrent chemoradiotherapy. The improvement in outcome seen with a concurrent chemoradiotherapy approach may be because of spatial cooperation, enhanced radiosensitization, and/or enhanced cytotoxicity. The taxanes, specifically paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), delivered in combination with radiation have been extensively examined in both preclinical and clinical studies. Several mechanisms have been suggested to explain the enhanced tumor cell kill seen with paclitaxel and radiation, and phase II studies have examined this combination in the setting of inoperable stage III non-small cell lung cancer. This review will explore some of the studies with this treatment approach in locally advanced disease. We also will briefly discuss some of the ongoing trials that are attempting to refine the delivery of concurrent thoracic radiation and paclitaxel-based chemotherapy., (Copyright 2001 by W.B. Saunders Company.)

The plant-derived taxanes have a unique mechanism of cytotoxic action and have shown interesting response and survival data in metastatic non-small cell lung cancer (NSCLC). Based on these results, taxane-based regimens have been investigated in combination with radiotherapy in unresectable NSCLC. Trials with paclitaxel-based concurrent chemoradiotherapy have shown 50-100% tumour response rates, 12-26 month median survivals and 32-52% 2-year survival rates. Trials with concurrent chemoradiotherapy with docetaxel have shown 35-92% tumour response rates, 12-23 month median survivals, and 41-43% 2 year survival rates. Taxane-based concurrent chemoradiotherapy for stage III NSCLC appears promising. Large ongoing randomised trials will define the role of these agents in the treatment of locally advanced NSCLC.

The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar, CPT-11)--offers the hope of advances against this malignancy. Irinotecan, a camptothecin derivative, has shown impressive activity in a variety of solid tumors, including non-small-cell lung cancer. It is believed to act by stabilizing the topoisomerase-DNA complex formed during diverse cellular processes, including replication and transcription. A considerable body of evidence also demonstrates that camptothecin and its derivatives possess substantial radiosensitization properties. This article will review the in vitro and in vivo data on irinotecan's ability to render tumors more susceptible to ionizing radiation. It will then focus on experience with irinotecan and thoracic radiation in the treatment of non-small-cell lung cancer, which has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies--such as the combination of radiation and irinotecan in lung cancer--will significantly impact cure rates in the future.