Rimner, Andreas

AbstractBackgroundCALGB 30610 trial demonstrated that once daily thoracic radiotherapy (TRT) was not superior compared to standard twice daily TRT, in patients with limited stage small cell lung cancer. Quality of life outcomes may help oncologists decide the best treatment approach.MethodsA total of 417 patients on CALGB 30610 participated in the quality‐of‐life substudy (CALGB 70702), which included the FACT Trial Outcome Index‐Lung Cancer (FACT‐L TOI), FACT‐Esophageal Cancer (FACT‐E) Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), difficulty swallowing, EQ‐5D, and treatment convenience assessment at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting TRT. Primary end points included FACT‐L TOI and FACT‐E at 12 weeks. Mean changes from baseline were compared between arms using general linear mixed models.ResultsFACT‐L worsening was more in the twice daily arm at week 3 (–1.0 vs. –7.0). FACT‐L TOI worsening was less at week 3 (–2.9 vs. –7.6) and greater at week 12 (–7.6 vs. –2.8) in the once daily arm. The once daily arm had a lower EQ‐5D index worsening at 3 weeks (0.01 vs. –0.02). Increase in acute esophagitis score (1.06 vs. 2.89; p < .001) and difficulty swallowing (0.39 vs. 1.14) were greater in the twice daily arm at week 3. A total of 74.5% of patients on the once daily arm felt that treatment was convenient, compared to 67% of patients in the twice daily arm (p = .03).ConclusionsThe once daily arm had better quality‐of‐life scores earlier during treatment and was perceived to be more convenient.

8504 Background: The CALGB 30610 trial demonstrated that 70Gy QD TRT was not associated with a superior overall survival compared to standard BID 45Gy TRT in limited stage small cell lung cancer. Since both arms appeared to provide similar clinical benefit, other factors such as quality of life may help oncologists decide on the best treatment approach for their patients. The present analysis was conducted to compare patients’ quality of life between these regimens in terms of their physical symptoms, physical functioning and psychological state. Methods: In the CALGB 30610 planned sub-study CALGB 70702, patients were administered the FACT-L, FACT Trial Outcome Index-Lung Cancer (FACT-L TOI), FACT-Esophageal Cancer Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), the EQ-5D at baseline and a single item assessing difficulty swallowing at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting radiation therapy. Patients were also asked to assess treatment inconvenience at these time points. The primary endpoints of CALGB 70702 were FACT-L TOI and FACT eating and swallowing subscales at 12 weeks. Mean changes from baseline were compared between arms using general linear mixed models. Results: 417 patients consented to participate in the patient-reported outcomes substudy. The completion rate of the questionnaires was 87% at baseline and 71% at week 52. The FACT-L total score mean worsening was significantly less in the QD arm compared to the BID arm at week 3 (-1.0 vs -7.0; P=.003), and marginally less at week 5 (-5.3 vs -11.0; P=.06). The FACT-L TOI mean worsening was significantly less in the QD arm than in the BID arm at week 3 (-2.9 vs -7.6; P=.003) and greater at week 12 (-7.6 vs -2.8; P=.03). The QD arm also had a lesser EQ-5D index mean worsening at 3 weeks (-0.04 vs 0.03; P=.002). Mean increase in the acute esophagitis score (1.06 vs 2.89; P<.001) and difficulty swallowing (0.39 vs 1.14; P<.001) were significantly greater in the BID arm at week 3. Mean worsening in HADS anxiety was significantly less in the QD arm at week 5 (-1.99 vs -0.95; P=.03). There were no other significant differences at the remaining timepoints between the two arms. Across visits on the QD arm, patients felt that treatment was inconvenient at 26% (96/376) assessments, compared to 33% (116/352) in the BID arm (chi-sq P=.03). Conclusions: Both radiation regimens were well tolerated. However, the QD arm had better quality of life scores at week 3 and was perceived to be less inconvenient. Clinical trial information: NCT00632853.

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.

TPS9079 Background: Pleurectomy/Decortication (P/D) with neoadjuvant or adjuvant chemotherapy has become a common lung-sparing surgical approach for MPM. Adjuvant hemithoracic IMPRINT was developed at Memorial Sloan Kettering Cancer Center and safe in a multi-institutional phase II study, with promising survival outcomes. The National Cancer Institute (NCI) sponsored this phase III randomized cooperative group trial to test the efficacy of this lung-sparing trimodality approach for resectable MPM. Methods: Patients with newly diagnosed MPM amenable to P/D are enrolled and undergo P/D followed by adjuvant platinum/pemetrexed (preferred) or neoadjuvant chemotherapy followed by P/D. Patients are stratified by histologic subtype, resection status (R0/1 vs. R2), and center patient volume (≤10 vs. > 10 P/Ds per year). Within 8 weeks after completion of the second modality patients are randomized 1:1 to undergo hemithoracic IMPRINT vs. no further therapy. All IMPRINT contours and treatment plans will be centrally reviewed. A contouring atlas and treatment planning constraints for target structures and organs at risk including acceptable and unacceptable variations and deviations were developed. Photon and proton therapy are permitted. The primary endpoint of the study is overall survival. Secondary endpoints include local failure-free, distant-metastases-free and progression-free survival, treatment-related toxicities (CTCAE v5.0) and change in quality-of-life (EORTC QLQ-C30 mean score changes at 9 months post randomization). The target accrual is 150 patients. This study was activated on January 29, 2020. Over 20 institutions have already committed to opening the study which is open to all National Clinical Trials Network (NCTN) sites. Treatment planning guidelines and helpful hints for photon and proton therapy will be presented. Conclusions: NRG LU-006 (clinicaltrials.gov: NCT04158141 ) is open to accrual. This is the first NRG Oncology randomized phase III trial on MPM and evaluates the use of IMPRINT following lung-sparing P/D and chemotherapy. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI). Clinical trial information: NCT04158141.