Prospective Radiologic-Pathologic Correlation of Macroscopic Volume and Microscopic Extension of Nonsolid Lung Nodules on Thin-section CT Images for Sublobar Resection and Stereotactic Radiotherapy Planning.

INTRODUCTION: The objective of this study was to determine whether computed tomography (CT) could be a useful tool for nonsolid lung nodule (NSN) treatment planning, surgery or stereotactic body radiation therapy (SBRT), by assessing the macroscopic and microscopic extension of these nodules. METHODS: The study prospectively included 23 patients undergoing anatomic resection at the Foch Hospital in 2020/2021 for NSN with a ground-glass component of more than 50%. Firstly, for each patient, both the macroscopic dimensions of the NSN were assessed on CT and during pathologic analysis. Secondly, the microscopic extension was assessed during pathologic examination. Wilcoxon sign rank tests were used to compare these dimensions. Spearman correlation test and Bland-Altman analysis were used to evaluate the agreement between radiological and pathologic measurements. RESULTS: On CT, the median largest diameter and volume of NSN were 21 mm and 3780 cc, while on pathologic analysis, they were 15 mm and 1800 cc, respectively. Therefore, the largest diameter and volume of the NSN were significantly higher on CT than on pathological analysis. For microscopic extension, the median largest diameter and volume of NSN were 17 mm and 2040 cc, respectively. No significant difference was observed between the macroscopic size and the microscopic extension assessed during pathologic analysis. Moreover, correlation analysis and Bland-Altman plots showed that radiological and pathologic measurements could provide equivalent precision. CONCLUSION: Our study showed that CT did not underestimate the macroscopic size and microscopic extension of NSN and confirmed that CT can be used for NSN treatment planning.

Radiotherapy mucositis in head and neck cancer: prevention by low-energy surface laser.

BACKGROUND: Modern radiotherapy (RT) planning techniques and the use of oral supportive care have reduced the occurrence of acute radiation-induced toxicities. Oral mucositis remains a major concern in patients with head and neck cancer as it can compromise treatment compliance and outcome. OBJECTIVE: To report the rate of mucositis with the preventive use of surface low-level laser therapy in patients with head and neck cancer. METHODS: Forty patients treated with definitive (n=27) or adjuvant (n=13) RT using volumetric arc therapy between August 2014 and October 2015 for squamous cell carcinoma of the head and neck were included. All patients were treated using photobiomodulation using surface low-level laser therapy (Heltschl kind FL 3500, 350 mW), 3 times a week during the whole treatment course. The grade of mucositis was obtained from week 1 to week 7 and at 1 month. RESULTS: The median RT dose was 70 Gy (64-70). Concomitant chemotherapy was administered in 29 patients. According to the Common Terminology Criteria for Adverse Events (CTCAE) v. 3, grade 0, 1, 2 and 3 mucositis was observed in 9 (22.5%), 9 (22.5%), 16 (40%) and 6 (15%) patients at week 7, and 32 (80%), 2 (5%), 3 (7.5%) and 3 (7.5%) patients at 1 month following treatment. No grade 4 occurred. Median average and maximum dose to the oral mucosa was 42 Gy (12.9-66.3) and 66.6 Gy (39-76), respectively. CONCLUSION: Despite a substantial dose to the oral mucosa, the rate of acute radiation-induced mucositis of grade ≥3 remains low in patients receiving extraoral low-energy laser during RT.

Efficacy of Large Use of Combined Hypofractionated Radiotherapy in a Cohort of Anti-PD-1 Monotherapy-Treated Melanoma Patients.

To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, 50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan−Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1−2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% [95% CI: 26.1−38.9]) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 [13.4−26.6] and 37.0 months [24.6−NA], respectively, in radiated patients, and 2.2 [1.5−2.6] and 4.3 months [2.6−7.1], respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6−25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.

Efficacy and Safety of Combined Brain Stereotactic Radiotherapy and Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with Brain Metastases.

BACKGROUND: To analyze the outcomes of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with immunotherapy (IT) and stereotactic radiotherapy (SRT) and to study the impact of the sequence between the two modalities. METHODS: The authors reviewed the records of 51 patients with 84 BM from NSCLC treated at Institut Curie with IT and SRT. BM were categorized into three groups: 'SRT before IT', 'concurrent SRT and IT', and 'SRT after IT.' Regional progression-free interval (R-PFI) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: After a median follow-up from SRT of 22.5 months (2.7-47.3), the 1-year and 2-year OS were 69.7% (95%CI [58.0-83.8]) and 44.0% [30.6-63.2], respectively. Concerning distant intracranial control, the 1-year and 2-year R-PFI were 40.1% [30.1-53.3] and 35.2% [25.1-49.4], respectively. Moreover, one-year R-PFI in 'SRT before IT', 'concurrent SRT and IT', and 'SRT after IT' groups were 24.1%, 49.6%, and 34.2%, respectively (p = 0.094). The type of therapeutic sequence did not appear to impact the risk of brain necrosis. CONCLUSIONS: The concurrent administration of SRT and IT appeared to offer the best locoregional control, without increasing the risk of toxicity, compared to patients treated with SRT before or after IT.

Perspective: Do Fasting, Caloric Restriction, and Diets Increase Sensitivity to Radiotherapy? A Literature Review.

Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor for the success of this therapy. A systematic review was performed via a PubMed search on RT and fasting, or caloric restriction, ketogenic diet (>75% of fat-derived energy intake), protein starvation, amino acid restriction, as well as the Warburg effect. Twenty-six eligible original articles (17 preclinical studies and 9 clinical noncontrolled studies on low-carbohydrate, high-fat diets popularized as ketogenic diets, representing a total of 77 patients) were included. Preclinical experiments suggest that a short period of fasting prior to radiation, and/or transient caloric restriction during treatment course, can increase tumor responsiveness. These regimens promote accumulation of oxidative lesions and insufficient repair, subsequently leading to cancer cell death. Due to their more flexible metabolism, healthy cells should be less sensitive, shifting their metabolism to support survival and repair. Interestingly, these regimens might stimulate an acute anticancer immune response, and may be of particular interest in tumors with high glucose uptake on positron emission tomography scan, a phenotype associated with poor survival and resistance to RT. Preclinical studies with ketogenic diets yielded more conflicting results, perhaps because cancer cells can sometimes metabolize fatty acids and/or ketone bodies. Randomized trials are awaited to specify the role of each strategy according to the clinical setting, although more stringent definitions of proposed diet, nutritional status, and consensual criteria for tumor response assessment are needed. In conclusion, dietary interventions during RT could be a simple and medically economical and inexpensive method that may deserve to be tested to improve efficiency of radiation.

Prognostic Impact of Residual HPV ctDNA Detection after Chemoradiotherapy for Anal Squamous Cell Carcinoma.

Purpose: Chemoradiotherapy (CRT) is the current standard of care for patients diagnosed with locally advanced anal squamous cell carcinoma (ASCC), but some patients develop local and/or distant relapse during follow-up. This study was designed to monitor human papillomavirus (HPV) circulating tumor DNA (ctDNA) levels during CRT in patients with ASCC.Experimental Design: We analyzed samples from patients with HPV16- or HPV18-positive locally advanced ASCC. Blood samples were collected before and after CRT. HPV16 or HPV18 ctDNA detection was performed by droplet digital-PCR.Results: HPV ctDNA was detected before CRT in 29 of 33 patients with stages II-III ASCC [sensitivity: 88%; 95% confidence interval (CI), 72-95]; ctDNA positivity rate was associated with tumor stage (64% and 100% in stages II and III, respectively; P = 0.008). Among ctDNA-positive patients at baseline, ctDNA levels were higher in N+ than in N- tumors (median 85 copies/mL, range = 8-9,333 vs. 32 copies/mL, range = 3-1,350; P = 0.03). ctDNA detection at baseline had no significant prognostic impact. After CRT, three of 18 (17%) patients displayed residual detectable HPV ctDNA; ctDNA detection after CRT was strongly associated with shorter disease-free survival (P < 0.0001).Conclusions: This is the first proof-of-concept study assessing the prognostic value of ctDNA after CRT in locally advanced ASCC. In most patients, HPV ctDNA can be detected before CRT and becomes undetectable during CRT. In this study, we show that residual ctDNA levels after CRT are associated with very poor outcome. Clin Cancer Res; 24(22); 5767-71. ©2018 AACR.