Analysis of Radiation Therapy Quality Assurance in NRG Oncology RTOG 0848.

PURPOSE: NRG/Radiation Therapy Oncology Group 0848 is a 2-step randomized trial to evaluate the benefit of the addition of concurrent fluoropyrimidine and radiation therapy (RT) after adjuvant chemotherapy (second step) for patients with resected pancreatic head adenocarcinoma. Real-time quality assurance (QA) was performed on each patient who underwent RT. This analysis aims to evaluate adherence to protocol-specified contouring and treatment planning and to report the types and frequencies of deviations requiring revisions. METHODS AND MATERIALS: In addition to a web-based contouring atlas, the protocol outlined step-by-step instructions for generating the clinical treatment volume through the creation of specific regions of interest. The planning target volume was a uniform 0.5 cm clinical treatment volume expansion. One of 2 radiation oncology study chairs independently reviewed each plan. Plans with unacceptable deviations were returned for revision and resubmitted until approved. Treatment started after final approval of the RT plan. RESULTS: From 2014 to 2018, 354 patients were enrolled in the second randomization. Of these, 160 patients received RT and were included in the QA analysis. Resubmissions were more common for patients planned with 3-dimensional conformal RT (43%) than with intensity modulated RT (31%). In total, at least 1 resubmission of the treatment plan was required for 33% of patients. Among patients requiring resubmission, most only needed 1 resubmission (87%). The most common reasons for resubmission were unacceptable deviations with respect to the preoperative gross target volume (60.7%) and the pancreaticojejunostomy (47.5%). CONCLUSION: One-third of patients required resubmission to meet protocol compliance criteria, demonstrating the continued need for expending resources on real-time, pretreatment QA in trials evaluating the use of RT, particularly for pancreas cancer. Rigorous QA is critically important for clinical trials involving RT to ensure that the true effect of RT is assessed. Moreover, RT QA serves as an educational process through providing feedback from specialists to practicing radiation oncologists on best practices.

Nanoparticle Albumin-bound Paclitaxel Plus Carboplatin Induction Followed by Nanoparticle Albumin-bound Paclitaxel Maintenance in Squamous Non-Small-cell Lung Cancer (ABOUND.sqm): A Phase III Randomized Clinical Trial.

BACKGROUND: We evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non-small-cell lung cancer. PATIENTS AND METHODS: Patients with treatment-naive squamous non-small-cell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m2 on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS). RESULTS: Overall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator's discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC and 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median follow-up, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P = .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nab-paclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in ≥ 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC). CONCLUSIONS: The results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC.

Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.

Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.

nab-paclitaxel/carboplatin induction in squamous NSCLC: longitudinal quality of life while on chemotherapy.

BACKGROUND: Longitudinal data on the impact of treatment on quality of life (QoL) in advanced non-small cell lung cancer (NSCLC) are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ≤4 cycles of nab-paclitaxel/carboplatin combination chemotherapy. METHODS: Patients received nab-paclitaxel 100 mg/m2 days 1, 8, 15 + carboplatin area under the curve 6 mg•min/mL day 1 (q3w) for four cycles. QoL was assessed by the Lung Cancer Symptom Scale (LCSS) and Euro-QoL-5 Dimensions-5 Levels (EQ-5D-5L) at baseline and each cycle (day 1). RESULTS: Two-hundred and six lesion-response-evaluable patients completed baseline + ≥1 postbaseline QoL assessment and were QoL evaluable. LCSS average total score and symptom burden index improved from baseline throughout four cycles. In the LCSS pulmonary symptoms score, 46% of patients reported clinically meaningful improvement (≥10 mm visual analog scale) from baseline. Individual EQ-5D-5L dimensions remained stable/improved in ≥83% of patients; ≈33% reported complete resolution of baseline problems at least once during four cycles. Generally, responders (unconfirmed complete/partial response) had higher scores vs nonresponders. CONCLUSION: In patients with squamous NSCLC, four cycles of nab-paclitaxel/carboplatin demonstrated clinically meaningful QoL improvements, with greater benefits in responders vs nonresponders.

Neoadjuvant Gemcitabine Chemotherapy followed by Concurrent IMRT Simultaneous Boost Achieves High R0 Resection in Borderline Resectable Pancreatic Cancer Patients.

BACKGROUND: To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability. METHODS: We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC. During the concurrent, chemo was 5-FU and radiation were IMRT with SIB technique to target the key areas with dose escalation to 5600 in 28 fractions. The key areas were defined by PET positive area. This was followed by restaging imaging to rule out distant metastases before resection. RESULTS: 25 finished dose escalation protocol. 2 of the 25 cases developed distant metastases, 23 (92%) patients without distant metastases underwent pancreatectomy. Among the those received pancreatectomy, 22 (95%) achieved negative margin (R0). The gastrointestinal toxicity > grade 2 was 8% and there was no grade 4 toxicity. CONCLUSION: Neoadjuvant Gemcitabine-based induction chemotherapy followed by 5-FU-based IMRT-SIB is a feasible option in improving the likelihood of R0 resection rate in BRPC without compromising the organs at risk for toxicity.