•Planning on multiple anatomic scenarios could improve CIRT robustness for pancreatic cancer.•The PRV approach fails in predicting duodenum position along the RT course.•Efficient online adaptation ...is needed to guarantee CIRT quality for pancreatic cancer.
To quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer.
For 10 previously treated patients, 4DCTs were acquired around −15 (CTPlan), −5 (RE1), −1 (RE2) and +6 (RE3) days from RT start. Treatment plans were newly optimized to a dose prescription of 38.4 Gy(RBE) (8 fractions) with a constraint of 38 Gy(RBE) to 1% of the gastrointestinal organs at risk volume (D1%). Three strategies were tested: (A) robust optimization on CTPlan maximum exhale (0Ex) with 3 mm set-up, 3% range uncertainty, including 30%-inhale; (B) addition of the RE1-0Ex scenario; (C) plan recalculation at each REi and adaptation (RPi) according to deviation thresholds from clinical goals. The cumulative variation of target coverage and GI-OARs doses was evaluated. Duodenum contours of all 4DCTs of each patient were registered on CTPlan-0Ex. The capacity of pre-RT acquisitions to predict duodenum position was investigated by computing the intersection of contours at CTplan, RE1, or their union, with respect to subsequent 4DCTs and the CTV, coupled with increasing margin.
(A) No recalculation exceeded the D1% constraint. (B) The inclusion of RE1-0Ex in the optimization problem improved inter-fraction robustness on a patient-specific basis, but was non-significant on average. (C) Half of the plans would be re-optimized to recover target coverage and/or minimize duodenum dose, at least once. A significant difference was observed between pre-RT duodenum contours when intersecting subsequent contours, either with a margin expansion.
Anatomical variations highlighted at multiple REi proved that a fast and efficient online adaptation is essential to optimize treatment quality of CIRT for pancreatic cancer.
Humeral heads can be unintentionally exposed during breast radiotherapy, particularly when regional lymph nodes are targeted. Moreover, rotational intensity-modulated radiation therapy techniques, ...such as helical tomotherapy (HT), increase the low-dose bath, the consequences of which are subject to debate. The aim of this study was to analyze late adverse events involving humeral heads occurring after adjuvant locoregional breast radiotherapy with HT. This single-center retrospective study included 159 breast cancer patients locoregionally irradiated, including the regional lymph nodes, in an adjuvant setting with HT at Institut Curie (Paris, France), between January 2010 and 2016. After a median delay of 48 months, six patients (3.8%) developed localized bone pain, three (1.9%) developed a shoulder functional limitation and one (0.6%) developed a traumatic humeral head fracture. The average mean and maximum doses to humeral heads were 9.18 Gy and 24.41 Gy, respectively, and were not statistically associated with humeral head adverse events. Adverse events were statistically more frequent after mastectomy than after breast-conserving surgery. Berg's level 1 and 2/3 irradiation, and right-sided radiotherapy were associated with an increased maximum dose. In summary, clinical adverse events were rare, and radiation exposure to humeral heads was low. No correlation was found between dosimetric parameters and late toxicity.
Background: Despite the large use of inhibitors of Poly-ADP ribose polymerase (PARP-I), the feasibility and safety of their combination with radiotherapy (RT) is unclear. Aim: We conducted a ...literature analysis with the aim to evaluate the efficacy and safety profile of a combination with RT and PARP-I. Method: The key issues for the current review were expressed in two questions according to the Population, Intervention, Control, Outcome (PICO) criteria: 1. What is the outcome and 2. What is the toxicity in patients treated with a combination of PARP-I and RT for a newly diagnosed or recurrent tumors? Results: A total of 12 clinical studies met the inclusion criteria including seven single-arm dose-escalation phase I studies, two phase II (two- and three-arms controlled trials) trials, one parallel-arm phase I study, and two phase I/II studies published between 2015 and 2021. RT was performed with photon beams and several schedules according to the clinical situation. The acute toxicity ≥ grade 3 ranged between 25% and >96%, which was divided into hematological or non-hematological adverse events. Conclusions: despite the heterogeneity of the evaluated patient populations and tumor types, and the limited number of the studies, this review suggests that a combination approach is feasible even though the efficacy profile remains unclear.
Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 ...trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% 95%CI: 69.8-99.8% with a 2-year PFS of 75% 95% CI: 56.5-99.5%. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3
T cells to PD-L1
tumor cells and of FOXP3
T cells to proliferating CD11c
myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4
T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted.
The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for ...the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.
Background: The combination of pertuzumab and trastuzumab dual HER2 blockade with concomitant curative dose locoregional breast radiotherapy in patients with metastatic breast cancer is an important ...part of treatment strategy. Methods: This was a retrospective study conducted at the Institut Curie on all patients treated concomitantly with pertuzumab/trastuzumab and locoregional breast radiotherapy. Toxicity was evaluated according to the NCICTCAEv4.0. Overall survival, progression-free survival and locoregional recurrence-free survival were evaluated in metastatic patients who were initially well controlled by chemotherapy, for whom local treatment was decided by the multidisciplinary team. Results: Fifty-five patients treated between October 2013 and December 2019 were included, with a median follow-up of 4.1 years. The median age was 53 years (range: 28–81). All patients received curative dose radiotherapy (RT) concomitantly with pertuzumab and trastuzumab (Pertu/Trastu). The median radiation dose was 50 Gy. Safety evaluation did not reveal any significant adverse effects, with 3 cases of grade 3 radiodermatitis (5.4%), but no significant gastrointestinal or cardiac toxicity. The mean difference in LVEF before any chemotherapy and after radiotherapy was −2.43% (p < 0.01). Conclusions: This study demonstrates that the combination of locoregional breast RT with dual HER2 blockade by Pertu/Trastu was very well tolerated, suggesting that RT can be safely administered to patients with HER2-positive breast cancer.
...the reliability of SLNB after neoadjuvant chemotherapy to affirm an ypN0 status is subject to intense debate: it has been suggested that the frequency of false-negative findings in this context ...was not negligible, reaching up to 12·6% in the ACOSOG Z1071 trial.4 However, combining SLNB and removal of the nodes, which were initially clipped during the baseline radiological evaluation, could lower the false-negative rate to 2·0%.5 Nevertheless, the results of the RAPCHEM study suggest that patients with a pathological complete response to neoadjuvant chemotherapy on SLNB could be safely treated without any axillary management, thus reducing to a minimum the risk of lymphoedema. For patients with two or fewer positive SLNBs, the ACOSOG Z11 trial6 showed that ALND could be safely replaced by axillary radiotherapy after breast-conserving surgery. ...the RAPCHEM protocol logically proposed to treat patients with ypN1 tumours on SLNB with axillary radiotherapy. ...the 7% locoregional relapse absolute risk reduction observed in this trial was much smaller than the historical 17% risk reduction reported by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis.8 Additionally, subgroup analyses showed that there was no significant benefit in case of hormone-receptor-negative HER2-positive tumours.
Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, ...first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the lung or the breasts) when treating mediastinal HL; consequently, secondary cancers, and cardiac and lung toxicity were substantially increased. Fortunately, HL RT has drastically evolved and, nowadays, state-of-the-art RT techniques efficiently spare critical organs-at-risks without altering local control or overall survival. Recently, proton therapy has been evaluated for mediastinal HL treatment, due to its possibility to significantly reduce integral dose to OARs, which is expected to limit second neoplasm risk and reduce late toxicity. Nevertheless, clinical experience for this recent technique is still limited worldwide. Based on current literature, this critical review aims to examine the current practice of proton therapy for mediastinal HL irradiation.
PDF
