Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group.

Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.

Helical tomotherapy and volumetric modulated arc therapy: New therapeutic arms in the breast cancer radiotherapy.

AIM: To analyse clinical and dosimetric results of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) in complex adjuvant breast and nodes irradiation. METHODS: Seventy-three patients were included (31 HT and 42 VMAT). Dose were 63.8 Gy (HT) and 63.2 Gy (VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes (SCN) and internal mammary chain (IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort (7 mm vs 5 mm). RESULTS: For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC: 96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5% (HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2% (VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1% (HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9% (VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy (HT) and 4.6 ± 0.9 Gy (VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts. CONCLUSION: HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results.

PURPOSE: To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. MATERIAL AND METHODS: From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. RESULTS: All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. CONCLUSIONS: Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

Feasibility of accelerated partial breast irradiation with volumetric-modulated arc therapy in elderly and frail patients.

BACKGROUND: Accelerated partial breast irradiation (APBI) is an option for adjuvant radiotherapy according to ASTRO and ESTRO recommendations. Among the available techniques, volumetric-modulated arc therapy (VMAT) is attractive but has not been extensively studied for APBI. This study assessed its feasibility, tolerance and early oncological outcomes. METHODS: We analysed the data of nine patients (median age 74 years) with ten lesions (one bilateral cancer) treated from May 2011 to July 2012 with APBI using VMAT. The radiation oncologist delineated the surgical tumour bed, and added an 18 mm isotropic margin to obtain the planning target volume (PTV). The dose was 40 Gy prescribed in 4 Gy fractions given twice a day over five days. Patients were regularly followed for toxicities and oncological outcomes. RESULTS: Mean PTV was 100.0 cm(3) and 95 % of the PTV received a mean dose of 99.7 % of the prescribed dose. Hot spots represented 0.3 % of the PTV. 6.2 %, 1.6 % and 0.3 % of the ipsilateral lung volume received 5 Gy (V5Gy), 10 Gy (V10Gy) and 20 Gy (V20Gy), respectively. Regarding the contralateral lung, V5Gy was 0.3 %, and V10Gy and V20Gy were nil. V5Gy accounted for 3.1 % of the heart. An average 580 monitor units were delivered. No acute or late grade ≥ 2 toxicities were observed. With a median follow-up of 26 months, no relapses occurred. CONCLUSION: In our study, VMAT allowed optimal dosimetry with consequential high therapeutic ratio in elderly and frail patients.

Role of the radiotherapy boost on local control in ductal carcinoma in situ.

Ductal carcinoma in situ of the breast is associated with low mortality rates, but local relapse is a matter of concern in this disease. Risk factors for local relapse include young age, close or positive margins, and tumor necrosis. Whole breast irradiation following breast-conserving surgery for ductal carcinoma in situ significantly reduces the risk of local relapse as compared to breast-conserving surgery alone. Studies point to similar outcomes between breast-conserving surgery plus radiotherapy and mastectomy, in the absence of extensive disease. A complementary boost to the surgical bed improves outcomes for patients with invasive breast cancer. However, the effect of this strategy has never been prospectively reported for ductal carcinoma in situ. Two randomized controlled trials assessing this issue are ongoing. This paper represents an update on available literature about radiotherapy for DCIS with a special focus on the role of a radiotherapy boost to the tumor bed.