Updates on the APBI-IMRT-Florence Trial (NCT02104895) Technique: From the Intensity Modulated Radiation Therapy Trial to the Volumetric Modulated Arc Therapy Clinical Practice.

Several phase 3 trials have demonstrated partial breast irradiation noninferiority compared with whole breast irradiation in terms of local control and similar or reduced toxicity. During recent years, especially owing to the COVID-19 pandemic, a growing interest in 5-fraction regimens emerged. The APBI-IMRT-Florence trial (NCT02104895) schedule (30 Gy in 5 fractions) might represent an appealing treatment option, being both a safe and effective partial breast irradiation schedule, with long-term reported results. The aim of this report is to support planners interested in implementing this technique and to warrant equal access to postoperative radiation treatment for most early breast cancer patient candidates. We report the current delivery technique optimized from the original protocol and the updated dose constraints for plan optimization. We also report a statistical analysis of dosimetric parameters on 50 patients treated in consecutive fractions. Treatment-related toxic effects were assessed using the acute radiation morbidity scoring criteria and late radiation morbidity scoring scheme from the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer. The mean volume of ipsilateral breast was 731 cm3 (standard deviation ± 450; range, 151-2205) and the mean planning target volume (PTV) was 139 cm3 (standard deviation ± 48; range, 55-259). There was good correlation between ipsilateral breast V15Gy and the ratio between the PTV and ipsilateral breast volume (R2 = .911). At a median follow-up of 4.5 years, 32% of patients (n = 16) developed any grade 1 acute toxic effect. No grade >1 toxic effect was observed. Sixteen percent of patients (n = 8) developed any grade 1 late toxic effect. No grade >1 toxic effect was observed. Physician-assessed cosmesis was reported as excellent (84%), good (14%), and fair (2%). The schedule of 30 Gy in 5 consecutive fractions might represent a safe, easy-to-deliver, and cost-effective option for appropriately selected patients affected by early breast cancer.

Durvalumab with cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: A phase 1/2 trial.

BACKGROUND AND PURPOSE: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma. MATERIALS AND METHODS: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and withdrawal of Durvalumab from supporting company, the study was prematurely terminated in April 2021. RESULTS: Between July 2019 and August 2020, 9 patients were enrolled in the study. All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for Cetuximab and Durvalumab, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported. At a median follow-up of 11.5 months (IQR 7.7-16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4). CONCLUSION: Albeit limited by the small sample size, our preliminary observation of anti-tumor activity and tolerability of Durvalumab in addition to Cetuximab and radiation may warrant further investigations.

Impact of COVID-19 on workload burden of a complex radiotherapy facility.

BACKGROUND AND PURPOSE: COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019. MATERIALS AND METHODS: Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11-April 24, 2019 (Fr/Hrs1), and March 11-April 24, 2020 (Fr/Hrs2). RESULTS: Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrsratio of 1.07 (95% CI 1.03-1.12, p = 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for SliR and PreciseR, with Fr/Hrsratio of 1.92 (95% CI 1.66-2.23, p < 0.0001) and 1.11 (95% CI 1.03-1.2, p = 0.003), respectively. No significant difference was reported for SynergyR and CyberknifeR with Fr/Hrsratio of 0.99 (95% CI 0.91-1.08, p = 0.8) and 0.9 (95% CI 0.77-1.06, p = 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for TomotherapyR, with Fr/Hrsratio of 0.88 (95% CI 0.8-0.96, p = 0.007). CONCLUSION: Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.

Management of prostate cancer radiotherapy during the COVID-19 pandemic: A necessary paradigm change.

PURPOSE: To adapt the management of prostate malignancy in response to the COVID-19 pandemic. METHODS: In according to the recommendations of the European Association of Urology, we have developed practical additional document on the treatment of prostate cancer. RESULTS: Low-Risk Group Watchful Waiting should be offered to patients >75 years old, with a limited life expectancy and unfit for local treatment. In Active Surveillance (AS) patients re-biopsy, PSA evaluation and visits should be deferred for up to 6 months, preferring non-invasive multiparametric-MRI. The active treatment should be delayed for 6-12 months. Intermediate-Risk Group AS should be offered in favorable-risk patients. Short-course neoadjuvant androgen deprivation therapy (ADT) combined with ultra-hypo-fractionation radiotherapy should be used in unfavorable-risk patients. High-Risk Group Neoadjuvant ADT combined with moderate hypofractionation should be preferred. Whole-pelvis irradiation should be offered to patients with positive lymph nodes in locally advanced setting. ADT should be initiated if PSA doubling time is < 12 months in radio-recurrent patients, as well as in low priority/low volume of metastatic hormone sensitive prostate cancer. If radiotherapy cannot be delayed, hypo-fractionated regimens should be preferred. In high priority class metastatic disease, treatment with androgen receptor-targeted agents should be offered. When palliative radiotherapy for painful bone metastasis is required, single fraction of 8 Gy should be offered. CONCLUSIONS: In Covid-19 Era, the challenge should concern a correct management of the oncologic patient, reducing the risk of spreading the virus without worsening tumor prognosis.