Radiation-Induced Emesis (RIE) in Extended-Field Radiotherapy for Gynecological Malignancies: Dosimetric and Non-Dosimetric Factors

Radiation-induced emesis (RIE) is usually noted during abdominal-pelvic radiotherapy. In gynecological malignancies, it is usually noted in para-aortic but not whole-pelvic irradiation. Irradiated small bowel (SB) may be associated with RIE. The significance of SB dosimetry remains unclear. Dosimetric and non-dosimetric factors were evaluated and correlated with RIE in 45 patients with gynecological malignancies undergoing extended-field radiotherapy (EFRT) (median 45 Gy) from 2006 to 2021. Early-onset RIE (within 72 h after the first fraction of EFRT) was noted in 10 of 12 RIE patients. RIE was significantly associated with the SB mean dose. The RIE rates were 58.3% and 15.2% (p = 0.007) in patients with a low (<63%) and high (≥63%) SB mean dose. Logistic regression revealed that the SB mean dose remained the independent factor of overall RIE (p = 0.049) and early-onset RIE (p = 0.014). Therefore, constraint of the SB mean dose limited to less than 63% of the prescribed dose is suggested to decrease RIE.

Intestinal mucositis precedes dysbiosis in a mouse model for pelvic irradiation

Pelvic radiotherapy is known to evoke intestinal mucositis and dysbiosis. Currently, there are no effective therapies available to mitigate these injuries, which is partly due to a lack of insight into the events causing mucositis and dysbiosis. Here, the complex interplay between the murine host and its microbiome following pelvic irradiation was mapped by characterizing intestinal mucositis along with extensive 16S microbial profiling. We demonstrated important morphological and inflammatory implications within one day after exposure, thereby impairing intestinal functionality and inducing translocation of intraluminal bacteria into mesenteric lymph nodes as innovatively quantified by flow cytometry. Concurrent 16S microbial profiling revealed a delayed impact of pelvic irradiation on beta diversity. Analysis of composition of microbiomes identified biomarkers for pelvic irradiation. Among them, members of the families Ruminococcaceae, Lachnospiraceae and Porphyromonadaceae were differentially affected. Altogether, our unprecedented findings showed how pelvic irradiation evoked structural and functional changes in the intestine, which secondarily resulted in a microbiome shift. Therefore, the presented in vivo irradiation-gut-microbiome platform allows further research into the pathobiology of pelvic irradiation-induced intestinal mucositis and resultant dysbiosis, as well as the exploration of mitigating treatments including drugs and food supplements.

Effects of irradiation doses <10 Gy and irradiated bone volume on the change in blood counts during and after pelvic irradiation

<p class="abstract"><strong>Background:</strong> Bone marrow is one of the organs at risk of complications during irradiation due to its radiosensitivity. Hematopoietic toxicity remains one of the main toxicities during irradiation of pelvis. Modern radiotherapy techniques, such as intensity modulation and three-dimensional conformal radiotherapy, allow for better dose compliance in target volumes while optimally sparing organs at risk. There is a lack of prospective studies and comparative trials specifying the dose constraints according to the presence or absence of chemotherapy and correlating with the patient’s bone marrow potential.</p><p class="abstract"><strong>Methods:</strong> This monocentric and prospective study conducted by the Strasbourg Europe Cancerology Institute aims to evaluate the hematological toxicity in patients treated with pelvic irradiation for prostate, rectum, anal canal, endometrium, or cervix cancer. One hundred patients will be included. The primary objective is to quantify the relationship between acute hematological toxicity and delivered doses and irradiated volumes in pelvic bone marrow for pelvic cancers. The prescribed dose to the pelvis depends on the tumor location, from 25 Gy in 5 fractions for rectal cancer to 78 Gy in 39 fractions for low-risk prostate cancer. Hematological toxicity will be measured by weekly blood count during radiotherapy and at one month and three months after the end of radiotherapy.</p><p class="abstract"><strong>Conclusions: </strong>The aim of this study is to improve and optimize radiotherapy if a dose limit or volume constraint is imposed by the results of the study. To our knowledge, this is the first study including several types of pelvic cancers and involving patients treated exclusively with radiotherapy, chemoradiotherapy or radiohormonotherapy.</p><p><strong>Trial Registration:</strong> Trial registration number is NCT04626466.</p>

Feeding the Controversy: When Pelvic Irradiation Improves Outcomes in High-Risk and Very High-Risk Prostate Cancer

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.