Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial.

OBJECTIVES: Chemo-radiotherapy (CRT) and concurrent PD-1 inhibition has shown promising results in pre-clinical models. So far, the feasibility of delivering concurrent CRT and PD-1/PD-L1 inhibition has never been assessed in a clinical trial. MATERIAL AND METHODS: NICOLAS is a phase-II trial evaluating the safety and efficacy of nivolumab combined with CRT in stage III NSCLC. Patients received 3 cycles of platinum-based chemotherapy and concurrent RT (66 Gy/33fractions). Nivolumab started concurrently with RT. The primary endpoint was 6-month post-RT rate of grade-≥3-pneumonitis. A formal interim safety analysis (IA) was scheduled when the first 21 patients reached 3 months follow-up post-RT. An early positive safety conclusion would be reached at IA if there were no grade ≥3-pneumonitis in those patients. Efficacy evaluation was planned provided the safety conclusion was reached. RESULTS AND CONCLUSION: As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade-≥3-pneumonitis was observed by the end of the 3-month post-RT follow-up period. The early safety IA provides evidence that the addition of nivolumab to concurrent CRT is safe and tolerable regarding the 6-month rate of pneumonitis grade ≥3 at the one-sided significance level of 5%. Following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort. NICOLAS trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent CRT in larger prospective trials for locally advanced NSCLC.

Assessment of cardiac exposure in left-tangential breast irradiation.

PURPOSE: To assess the value of treatment-planning related parameters namely, the breast volume; the distance of the inferior field border to diaphragm; and the cardiothoracic ratio for left-tangential breast irradiation. PATIENTS AND METHODS: Treatment plans of 27 consecutively left-sided breast cancer patients after breast conserving surgery were evaluated for several parameters concerning heart-irradiation. We measured the heart distance respective to the cardiothoracic ratio and the distance of the inferior field border to diaphragm, as well as the breast volume in correlation with the irradiated heart volume. RESULTS: The mean heart and left breast volumes were 504 cm(3) and 672.8 cm(3), respectively. The mean heart diameter was 13.4 cm; the mean cardiothoracic ratio 0.51 and the mean distance of the inferior field border to diaphragm was 1.4 cm. Cardiothoracic ratio (p=0.01), breast volume (p=0.0002), distance of the inferior field border to diaphragm (p=0.02) and central lung distance (p=0.02) were significantly correlated with the measured heart distance. A significant correlation was also found between cardiothoracic ratio, breast volume and distance of the inferior field border to diaphragm with the irradiated heart volume measured by V10, V20 and V40. CONCLUSION: The verification of parameters like cardiothoracic ratio, distance of the inferior field border to diaphragm and breast volume in left-sided breast cancer patients may help in determining which patients could benefit from more complex planning techniques such as intensity-modulated radiotherapy to reduced risk of late cardiac injury.

Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence.

AIM: Contribution of 3-phase 18F-fluorocholine PET/CT in suspected prostate cancer recurrence at early rise of PSA. PATIENTS, METHODS: Retrospective analysis was performed in 47 patients after initial treatment with radiotherapy (n=30) or surgery (n=17). Following CT, 10 minutes list-mode PET acquisition was done over the prostate bed after injection of 300 MBq of 18F-fluorocholine. Three timeframes of 3 minutes each were reconstructed for analysis. All patients underwent subsequent whole body PET/CT. Delayed pelvic PET/CT was obtained in 36 patients. PET/CT was interpreted visually by two observers and SUVmax determined for suspicious lesions. Biopsies were obtained from 13 patients. RESULTS: Biopsies confirmed the presence of cancer in 11 of 13 patients with positive PET for a total of 15 local recurrences in which average SUVmax increased during 14 minutes post injection and marginally decreased in delayed scanning. Conversely inguinal lymph nodes with mild to moderate metabolic activity on PET showed a clearly different pattern with decreasing SUVmax on dynamic images. Three-phase PET/CT contributed to the diagnostic assessment of 10 of 47 patients with biological evidence of recurrence of cancer. It notably allowed the discrimination of confounding blood pool or urinary activity from suspicious hyperactivities. PET/CT was positive in all patients with PSA>or=2 ng/ml (n=34) and in 4/13 patients presenting PSA values<2 ng/ml. CONCLUSION: 18F-fluorocholine 3-phase PET/CT showed a progressively increasing SUVmax in biopsy confirmed cancer lesions up to 14 minutes post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.

Carbogen breathing combined with radical radiotherapy in advanced head and neck cancer patients with severe co-morbidities.

AIMS: To assess the feasibility of carbogen breathing combined with radical radiotherapy in patients with advanced head and neck cancer who are unfit to receive concomitant chemotherapy. MATERIALS AND METHODS: Twenty patients (median age 66 years) with advanced squamous cell carcinoma of the head and neck were treated with either concomitant boost radiotherapy (75%) or mono-fractionated radiotherapy (25%) combined with carbogen breathing. The median tumour dose was 69.5 Gy. The main sites of disease were the oropharynx in 50%, the oral cavity in 15% and the hypopharynx in 30%. All but one patient had stage III (25%) or IV (70%) disease. The median follow-up for the surviving patients was 26 months (range 6-50 months). RESULTS: Carbogen breathing was well tolerated, permitting its delivery throughout the radiotherapy course. Three patients had treatment interruption because of acute toxicities (median 15 days; range 3-30 days). Grade 3 Radiation Therapy Oncology Group acute toxicity was observed in 80% of the patients (mainly mucositis), and nutritional support was required in eight patients (40%). Grade 2 late toxicity occurred in 30%; one patient presented with grade 4 late toxicity (bone necrosis). The 2-year actuarial locoregional control for all patients and for those treated with accelerated radiotherapy was 56% and 67%, respectively. The corresponding rates for disease-free survival were 45% and 53%. CONCLUSIONS: Considering the poor results of radiotherapy alone in advanced head and neck cancer, these results suggest that carbogen breathing may be a valid alternative for patients with severe co-morbidities who are unfit to receive concomitant chemotherapy.