CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial.

BACKGROUND: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA50-RR; ≥50% decrease from baseline). RESULTS: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7-55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7-58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0-11.6) and 18.2 (14.6-20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA50-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3-4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel). CONCLUSIONS: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. CLINICALTRIALS. GOV REGISTRATION: NCT03338790.

Nivolumab plus rucaparib for metastatic castration-resistant prostate cancer: results from the phase 2 CheckMate 9KD trial.

BACKGROUND: CheckMate 9KD (NCT03338790) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib. METHODS: CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0-1. Cohort A1 included patients with postchemotherapy mCRPC (1-2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 mg every 4 weeks plus rucaparib 600 mg two times per day (nivolumab dosing ≤2 years). Coprimary endpoints were objective response rate (ORR) per Prostate Cancer Clinical Trials Working Group 3 and prostate-specific antigen response rate (PSA50-RR; ≥50% PSA reduction) in all-treated patients and patients with homologous recombination deficiency (HRD)-positive tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. RESULTS: Outcomes (95% CI) among all-treated, HRD-positive, and BRCA1/2-positive populations for cohort A1 were confirmed ORR: 10.3% (3.9-21.2) (n=58), 17.2% (5.8-35.8) (n=29), and 33.3% (7.5-70.1) (n=9); confirmed PSA50-RR: 11.9% (5.9-20.8) (n=84), 18.2% (8.2-32.7) (n=44), and 41.7% (15.2-72.3) (n=12); median rPFS: 4.9 (3.7-5.7) (n=88), 5.8 (3.7-8.4) (n=45), and 5.6 (2.8-15.7) (n=12) months; and median OS: 13.9 (10.4-15.8) (n=88), 15.4 (11.4-18.2) (n=45), and 15.2 (3.0-not estimable) (n=12) months. For cohort A2 they were confirmed ORR: 15.4% (5.9-30.5) (n=39), 25.0% (8.7-49.1) (n=20), and 33.3% (7.5-70.1) (n=9); confirmed PSA50-RR: 27.3% (17.0-39.6) (n=66), 41.9 (24.5-60.9) (n=31), and 84.6% (54.6-98.1) (n=13); median rPFS: 8.1 (5.6-10.9) (n=71), 10.9 (6.7-12.0) (n=34), and 10.9 (5.6-12.0) (n=15) months; and median OS: 20.2 (14.1-22.8) (n=71), 22.7 (14.1-not estimable) (n=34), and 20.2 (11.1-not estimable) (n=15) months. In cohorts A1 and A2, respectively, the most common any-grade and grade 3-4 treatment-related adverse events (TRAEs) were nausea (40.9% and 40.8%) and anemia (20.5% and 14.1%). Discontinuation rates due to TRAEs were 27.3% and 23.9%, respectively. CONCLUSIONS: Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naïve mCRPC, particularly those harboring BRCA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial. TRIAL REGISTRATION NUMBER: NCT03338790.

Cardiac Monitoring for Thoracic Radiation Therapy: Survey of Practice Patterns in the United States.

OBJECTIVE: The American Society of Clinical Oncology (ASCO) 2017 guidelines on cardiac monitoring during cancer treatments identified patients receiving thoracic radiation (TRT) ≥30 Gy (heart in field) at increased risk for developing radiation-induced heart disease (RIHD). ASCO encouraged clinicians to actively screen and monitor for baseline modifiable cardiac risk factors and therapy-induced cardiotoxicity in this high-risk population. Coronary artery calcium (CAC) is an independent risk factor for adverse cardiac events that can be mitigated with preventative medical therapy. It is unclear whether radiation oncologists (ROs) are aware of ASCO guidelines or the implications of CAC observed on computed tomographic scans. We report on practice patterns, perceptions, and experiences of cardiac monitoring for patients receiving definitive TRT, excluding breast patients. MATERIALS AND METHODS: A 28-question survey was emailed to United States ROs 3 times from September 2018 to January 2019. RESULTS: There were 162 respondents from 42 states, 51% in academic practice. Most ROs (81%) were not aware of the ASCO guidelines. Only 24% agreed with the guidelines, only 27% believed symptomatic RIHD could manifest within 2 years of TRT, and 69% thought there was a lack of strong evidence for type and timing of cardiac monitoring tests. If CAC was evident on computed tomographic scans, 40% took no further action to inform the patient or referring doctor. CONCLUSIONS: This survey highlights a critical gap in knowledge about cardiac monitoring and potentially life-saving opportunities for preventive cardiac medical management. Future studies focusing on timing and detection of RIHD may elucidate the utility of cardiac monitoring for TRT patients.

Incidental Coronary Artery Calcium on Breast Radiation Therapy Planning Scans Identifies Patients for Cardiac Preventive Therapy.

PURPOSE/OBJECTIVE(S): The presence of coronary artery calcium (CAC>0) is associated with increased cardiac-related mortality and is a common indication to initiate statin therapy to prevent future long-term cardiac-related adverse events. CAC is also well visualized on noncontrast chest computed tomography simulation (CT sim) scans used for breast radiation planning. We hypothesize that by screening for incidental CAC on CT sims, radiation oncologists could help identify patients who may benefit from additional preventive medical interventions with their primary care physician or cardiologist. METHODS: A retrospective analysis of 126 consecutive patients with breast cancer treated with external beam radiation therapy at a single institution was performed. Noncontrast CT sim scans were reviewed for the presence of CAC and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated to identify patients who may benefit from initiating statin therapy. Patients with CAC>0 and/or ASCVD risk >20% were identified as those who may benefit from statin therapy. RESULTS: Out of 72 patients with CAC>0, only 12(16%) had reported pre-existing coronary artery disease and 32(44%) were not already on recommended statin therapy. CAC>0 visualized on CT sim was able to identify 29 additional patients who would benefit from statin beyond what the ASCVD risk calculator could identify. CONCLUSION: Observation of incidental CAC on breast radiation-planning CT scans identified patients who could benefit from cardiac-related preventive strategies. By increasing attention, awareness, and reporting of incidental CAC visible on CT sims, radiation oncologists may fulfill a unique role to bridge a potential gap in cardiovascular preventive medicine.

Concurrent Radiation and Immunotherapy: Survey of Practice Patterns in the United States.

OBJECTIVE: The objective of this study was to report on US radiation oncologists' (ROs) practice patterns and perceptions of concurrent radiation (RT) and immunotherapy (IT) (CRI). METHODS: A 22-question survey was emailed to radiation oncologists in February 2018. CRI was defined as RT completed within 1 week before initial IT infusion through 4 weeks after final IT infusion. RESULTS: Of the 323 respondents from 45 states, 88% had experience treating a patient with CRI, including 51% private and 48% academic physicians. The most common reason for not offering CRI was concerns of increased toxicity (50%). Although 84% to 94% of respondents did not change RT dose, more ROs decreased dose when treating central structures (chest/abdomen/pelvis) versus noncentral structures (brain/head and neck/extremities): 13% to 15% versus 4% to 8%, P<0.001. The majority (58% to 80%) of respondents would not delay RT from last IT infusion. Moderate and significant actual toxicities were rare (medical intervention 6%, hospitalization/death <1%). 97.5% of ROs did not routinely prescribed prophylactic steroids for CRI. More ROs believed CRI with SBRT/SRS versus palliative RT had better local control (35% vs. 25%, P<0.05) and higher rates of abscopal responses (41% vs. 25%, P<0.01). CONCLUSIONS: Despite concerns for toxicity, ROs with CRI experience reported minimal toxicities. Most ROs do not alter RT dose, use prophylactic steroids, or delay starting RT from last IT infusion. Uncertainty remains about improved local control outcomes and abscopal responses from CRI, with a perception that concurrent SBRT offers better outcomes than palliative RT. These survey results may help guide ROs until more definitive data are available.

Checkpoint Inhibition: Will Combination with Radiotherapy and Nanoparticle-Mediated Delivery Improve Efficacy?

Checkpoint inhibition (CPI) has been a rare success story in the field of cancer immunotherapy. Knowledge gleaned from preclinical studies and patients that do not respond to these therapies suggest that the presence of tumor-infiltrating lymphocytes and establishment of immunostimulatory conditions, prior to CPI treatment, are required for efficacy of CPI. To this end, radiation therapy (RT) has been shown to promote immunogenic cell-death-mediated tumor-antigen release, increase infiltration and cross-priming of T cells, and decreasing immunosuppressive milieu in the tumor microenvironment, hence allowing CPI to take effect. Preclinical and clinical studies evaluating the combination of RT with CPI have been shown to overcome the resistance to either therapy alone. Additionally, nanoparticle and liposome-mediated delivery of checkpoint inhibitors has been shown to overcome toxicities and improve therapeutic efficacy, providing a rationale for clinical investigations of nanoparticle, microparticle, and liposomal delivery of checkpoint inhibitors. In this review, we summarize the preclinical and clinical studies of combined RT and CPI therapies in various cancers, and review findings from studies that evaluated nanoparticle and liposomal delivery of checkpoint inhibitors for cancer treatments.

Multi-institutional report on toxicities of concurrent nivolumab and radiation therapy.

PURPOSE: Radiation therapy (RT) and nivolumab are standard therapies for a wide range of advanced and metastatic cancers, yet little is known about the toxicity profile of their combined treatment. The rate of grade ≥3 toxicities from nivolumab monotherapy and radiation-only palliative treatments has been reported at 10% to 18% and 0% to 26%, respectively. We reviewed our experience to assess the acute toxicity profile of concurrent RT-nivolumab. METHODS AND MATERIALS: A retrospective review of all consecutive patients from January 2015 to May 2017 who received concurrent RT-nivolumab was conducted at 4 separate centers. Concurrent RT-nivolumab was defined as RT completed between 3 days prior to initial nivolumab infusion and 28 days after the last nivolumab infusion. RESULTS: Of the 261 patients who received nivolumab, 46 (17.6%) had concurrent RT to 67 treatment sites. The median follow-up was 3.3 months (interquartile range, 1.7-6.1 months) and the 1-year overall survival rate was 22%. For the 11 of 46 patients (24%) who were alive at last analysis, the median follow-up was 12.8 months (interquartile range, 8.3-14.9 months). The most common histology, RT prescription, and treatment site were non-small cell lung cancer (23 of 46 patients; 50%), 30 Gy in 10 fractions (24 of 67 patients; 35.8%), and abdomen/pelvis (16 of 67 patients; 24%), respectively. Four patients with melanoma had concurrent ipilimumab and were removed from the final toxicity analysis of RT-nivolumab. Within 3 months of treatment with RT-nivolumab, 4 of 42 patients (9.5%) experienced grade 3 toxicity and 2 of these patients' toxicities were attributed specifically to the addition of RT: grade 3 hearing loss after whole brain RT and grade 3 pancreatitis after stereotactic body RT to the left adrenal gland. One death from transaminitis was attributed to nivolumab alone because the RT field did not encompass the liver. CONCLUSIONS: Concurrent RT-nivolumab did not appear to increase the toxicity profile from the previously reported toxicity rates from nivolumab or radiation alone.

Immunotherapy, Radiotherapy, and Hyperthermia: A Combined Therapeutic Approach in Pancreatic Cancer Treatment.

Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. In these advanced cases, chemotherapy and radiation have shown limited tumor control, and PC continues to be refractory to treatment and results in a poor survival outcome. In recent years, there has been intensive research on checkpoint inhibitor immunotherapy for PC, however, PC is characterized with dense stromal tissue and a tumor microenvironment (TME) that is highly immunosuppressive, which makes immunotherapy less effective. Interestingly, when immunotherapy is combined with radiation therapy (RT) and loco-regional hyperthermia (HT), it has demonstrated enhanced tumor responses. HT improves tumor killing via a variety of mechanisms, targeting both the tumor and the TME. Targeted HT raises the temperature of the tumor and surrounding tissues to 42⁻43 °C and makes the tumor more immunoresponsive. HT can also modulate the immune system of the TME by inducing and synthesizing heat shock proteins (HSP), which also activate an anti-tumor response. It is well known that HT can enhance RT-induced DNA damage in cancer cells and simultaneously help to oxygenate hypoxic regions. Thus, it is envisaged that combined HT and RT might have immunomodulatory effects in the PC-TME, making PC more responsive to immunotherapies. Moreover, the combined tripartite approach of immunotherapy, RT, and HT could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the immunotherapeutic effect of overall individual therapies to treat local and metastatic PC. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than monotherapy or dual therapy to treat and increase the survival of the PC patients.

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.

Helical Therapy is Safe for Lung Stereotactic Body Radiation Therapy Despite Limitations in Achieving Sharp Dose Gradients.

PURPOSE: We observed that many of our helical therapy lung stereotactic body radiation therapy plans did not meet the Radiation Therapy Oncology Group (RTOG) recommended R50% (volume of 50% of the prescription dose/planning target volume), which characterizes the steepness of dose fall off. We hypothesized that despite not meeting R50%, helical therapy lung stereotactic body radiation therapy plans would confer similar local control and minimal side effects as previously reported using nonhelical treatment platforms. MATERIALS AND METHODS: We report a retrospective review of all consecutive patients treated off-protocol with stereotactic body radiation therapy for peripheral lung lesions from 2008 to 2013 utilizing helical therapy. Seventy-four patients (81 lesions and 79 plans) were treated with doses ranging from 48 to 60 Gy in 3 to 5 fractions prescribed to the edge of the planning target volume. RESULTS: Forty-eight (61%) plans had major deviation from R50%. Only 1 (<1%) plan had a major deviation from the R100%. All plans had > 95% planning target volume coverage by prescription dose, 7(8.6%) plans with 121% to 133% maximum dose, and lung V20 Gy <10% in 70 (89%) plans. With a median follow-up of 4.7 years (95% confidence interval: 4.1-5.3), local control for all patients at 1, 2, and 5 years was 94.6%, 83.4%, and 74%, respectively. For patients with primary stage I-II lung cancer (n = 46), the 1, 2, and 5-year local control: 97.2%, 94.2%, and 86.9%; RC: 97.6%, 82.5%, and 69.5%; and DM: 3%, 16%, and 33.4%, respectively. Patients treated for lung metastases (n = 26) had worse local control at 1, 2, and 5 years: 94.4%, 69.3%, and 55.5%, respectively. Side effects were rare with 2 (3%) patients reporting chest wall pain and 6 (8%) patients experiencing radiation pneumonitis, including 1 patient who had grade 5 radiation pneumonitis. CONCLUSIONS: Helical therapy delivers a safe and effective lung stereotactic body radiation therapy plan, despite not being able to meet RTOG's recommended R50 conformality constraint.

Systematic review of the cost effectiveness of radiation therapy for prostate cancer from 2003 to 2013.

BACKGROUND: Prostate cancer remains a prevalent diagnosis with a spectrum of treatment choices that offer similar oncologic outcomes but differing side effect profiles and associated costs. As the technology for prostate radiation therapy has advanced, its associated costs have escalated, thus making cost-effectiveness analyses critical to assess the value of competing treatment options, including watchful waiting, surgery, brachytherapy, intensity-modulated radiation therapy (IMRT), 3D-conformal radiation therapy (3D-CRT), proton beam therapy (PBT), and stereotactic body radiation therapy (SBRT). OBJECTIVE: The aim of this systematic review was to identify articles that performed a cost-effectiveness analysis on different radiation treatment options for localized prostate cancer, summarize their findings, and highlight the main drivers of cost effectiveness. METHODS: A literature search was performed on two databases, PubMed and the Cost-Effectiveness Analysis Registry ( https://research.tufts-nemc.org/cear4 ), using search terms that included 'prostate', 'cost effectiveness prostate radiation' and 'cost analysis comparative effectiveness prostate radiation'. Studies were included in this review if the cost data were from 2002 or later, and outcomes reported both cost and effectiveness, preferably including a cost-utility analysis with the outcome of an incremental cost-effectiveness ratio with quality-adjusted life-year (QALY) as the effectiveness measure. RESULTS: There were 14 articles between 2003 and 2013 that discussed cost effectiveness of prostate radiotherapy in men over the age of 65. All but four of the papers were from the US; the others were from Canada and the UK. The majority of the papers used Markov decision analysis and estimated cost from a payer's perspective, usually from Medicare reimbursement data. Assumptions for the model and utilities to calculate QALYs were estimated using published literature at the time of the analysis. Each analysis had a sensitivity analysis to compensate for the uncertainty of the model inputs. The main drivers of cost effectiveness were the cost of the radiation treatment and the differential QALYs accrued because of different treatment-related morbidities. Brachytherapy was consistently found to be more cost effective when compared with surgery and other radiation treatment options. IMRT was cost effective when compared with 3D-CRT. PBT was not found to be cost effective in any of the analyses, mostly due to the high costs of PBT. SBRT was the newest technology that was analyzed, and it was also found to be cost effective compared with IMRT and PBT. CONCLUSIONS: Cost-effectiveness research of prostate radiation treatments allows patients, providers, and payers to better understand the true value of each treatment choice. Due to the variation in each of these analyses (e.g., costing, and disease and complication assumptions, etc.), it is difficult to generalize the results. One must be careful in drawing conclusions from these studies and extrapolating to individual patients, particularly with the clear utility dependence seen in the majority of these studies.

Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non-small cell lung cancer.

Patients with bulky non-small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were created for the prechemotherapy and postchemotherapy scans so as to deliver 60Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1cc (7.3 to 351.6cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.

Impact of induction chemotherapy on estimated risk of radiation pneumonitis in small cell lung cancer.

INTRODUCTION: Induction chemotherapy in patients with bulky small cell lung cancer (SCLC) could lead to decreased tumor burden, smaller radiation fields, and less pulmonary toxicity. This study compared radiation therapy (RT) plans based on pre- and postchemotherapy computed tomography (CT) scans of patients with SCLC to estimate the reduced risk of radiation pneumonitis (RP) after receiving chemotherapy. METHODS: Between 2003 and 2009, 23 patients with stage IV SCLC were treated with chemotherapy alone (no surgery or RT) and had computed tomography scans pre- and post two cycles of platin-based chemotherapy. Simulated RT plans were created as if to deliver 45 Gy to the thoracic disease. The percent of lung receiving ≥20 Gy (V20), mean lung dose, and normal tissue complication probability (NTCP) was evaluated in patients who had a partial response (≥30% volumetric reduction) in gross tumor volume. RESULTS: One (4.3%) patient had a complete response, 18 (78.3%) had a partial response, and four (17.4%) had stable disease. Among 18 responders, the absolute decrease in V20 was 7.4% (p < 0.01), in mean lung dose was 3.3 Gy (p < 0.01), and in NTCP was 5.5% (p < 0.01). Patients with a prechemotherapy V20 ≥35% versus V20 less than 35% had an average absolute reduction in NTCP of 10% versus 2% (p < 0.01). CONCLUSION: Patients with limited stage SCLC with a V20 ≥35% may benefit from induction chemotherapy as there is an estimated reduction of RP of 10%. This reduction in risk of RP after induction chemotherapy should be weighed against risks and benefits of delaying upfront RT.