Gynecologic Cancer Therapy Research Articles

Updates in the Use of Targeted Therapies for Gynecologic Cancers.

Targeted therapies have changed the treatment landscape in gynecologic cancer. Studies released over the past year have led to the incorporation of immunotherapy (IO) into the treatment for all patients with endometrial and cervical cancers at some point during their disease course. Poly(ADP-ribose) polymerase (PARP) inhibitors continue to play a role in women with ovarian carcinoma, particularly in homologous repair deficient tumors. Furthermore, the benefit of PARP inhibitors in challenging subgroups continues to be elucidated. Biomarker identification has led to the approval or compendium listing of several antibody-drug conjugates (ADCs). This review will update on IO, ADCs, and PARP inhibition for the treatment of gynecologic cancers.

Resveratrol in the Treatment of Gynecological Cancer: Mechanisms and Therapeutic Potential.

Gynecological cancers, encompassing endometrial, ovarian, and cervical cancer, pose significant challenges in clinical practice, often marked by high mortality rates and treatment resistance. Despite advances in standard therapies, including chemoradiation and surgery, tumor recurrence and metastasis remain formidable obstacles. In this context, there is a pressing need to explore novel therapeutic strategies that offer improved efficacy and reduced side effects. Herbal medicine, particularly compounds like resveratrol, has garnered attention for its diverse biological properties, including anticancer effects. Resveratrol, a multipotential nutraceutical, holds promise in gynecological cancer therapy through its modulation of key cellular and molecular processes. This review aims to provide an overview of the current status, challenges, and opportunities in utilizing resveratrol for gynecological cancer treatment. We discuss its role in miRNA regulation, clinical trial findings, and the development of effective formulations. By elucidating the underlying mechanisms of resveratrol's anticancer effects and exploring innovative delivery systems, we aim to shed light on the potential avenues for optimizing its therapeutic benefits in gynecological cancers.

Impact of Stimuli-Responsive Biomaterials in Gynecological Cancer Therapy

Impact of Stimuli-Responsive Biomaterials in Gynecological Cancer Therapy

Deep learning-based dose prediction to improve the plan quality of volumetric modulated arc therapy for gynecologic cancers.

In recent years, deep-learning models have been used to predict entire three-dimensional dose distributions. However, the usability of dose predictions to improve plan quality should be further investigated. To develop a deep-learning model to predict high-quality dose distributions for volumetric modulated arc therapy (VMAT) plans for patients with gynecologic cancer and to evaluate their usability in driving plan quality improvements. A total of 79 VMAT plans for the female pelvis were used to train (47 plans), validate (16 plans), and test (16 plans) 3D dense dilated U-Net models to predict 3D dose distributions. The models received the normalized CT scan, dose prescription, and target and normal tissue contours as inputs. Three models were used to predict the dose distributions for plans in the test set. A radiation oncologist specializing in the treatment of gynecologic cancers scored the test set predictions using a 5-point scale (5, acceptable as-is; 4, prefer minor edits; 3, minor edits needed; 2, major edits needed; and 1, unacceptable). The clinical plans for which the dose predictions indicated that improvements could be made were reoptimized with constraints extracted from the predictions. The predicted dose distributions in the test set were of comparable quality to the clinical plans. The mean voxel-wise dose difference was -0.14±0.46Gy. The percentage dose differences in the predicted target metrics of and were -1.05%±0.59% and 0.21%±0.28%, respectively. The dose differences in the predicted organ at risk mean and maximum doses were -0.30±1.66Gy and -0.42±2.07Gy, respectively. A radiation oncologist deemed all of the predicted dose distributions clinically acceptable; 12 received a score of 5, and four received a score of 4. Replanning of flagged plans (five plans) showed that the original plans could be further optimized to give dose distributions close to the predicted dose distributions. Deep-learning dose prediction can be used to predict high-quality and clinically acceptable dose distributions for VMAT female pelvis plans, which can then be used to identify plans that can be improved with additional optimization.

The Role of Bitter Melon in Breast and Gynecological Cancer Prevention and Therapy.

Phytotherapy has long represented a widely accepted treatment alternative to conventional therapy. Bitter melon is a vine with potent antitumor effects against numerous cancer entities. To date, no review article has, however, been published on the role of bitter melon in breast and gynecological cancer prevention and therapy. The current work constitutes the most comprehensive, up-to-date review of the literature, which highlights the promising anticancer effects of bitter melon on breast, ovarian, and cervical cancer cells and discusses future research recommendations.

Clinical Outcomes of Intensity Modulated Proton Therapy Reirradiation for Gynecologic Malignancies

Pelvic reirradiation (re-RT) for patients with gynecologic cancers remains a challenge because of toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients with re-RT to the pelvis/abdomen with intensity modulated proton therapy (IMPT) for gynecologic cancers. We performed a retrospective analysis of all patients with gynecologic cancer treated at a single institution between 2015 and 2021 with IMPT re-RT. Patients were included for analysis if the IMPT plan had at least partial overlap with the treated volume of a previous radiation treatment. A total of 29 patients were included for analysis, with 30 total courses of re-RT. The majority of patients had been treated previously with conventional fractionation to a median dose of 49.2 Gy (30-61.6 Gy). With a median follow-up of 23 months, 1-year local control was 83.5% and overall survival was 65.7%. Three patients (10%) developed acute and late grade 3 toxicity. One-year freedom from late grade 3+ toxicity was 96.3%. This is the first complete analysis of clinical outcomes for re-RT with IMPT for gynecologic malignancies. We demonstrate excellent local control and acceptable acute and late toxicity. IMPT should strongly be considered for treatments requiring re-RT for gynecologic malignancies.

A review of recent advances on single use of antibody-drug conjugates or combination with tumor immunology therapy for gynecologic cancer.

Immune checkpoint inhibitors have made significant progress in the treatment of various cancers. However, due to the low ICI responsive rate for the gynecologic cancer, ICI two-drug combination therapy tends to be a predominant way for clinical treatment. Antibody-drug conjugates, a promising therapeutic modality for cancer, have been approved by the FDA for breast cancer, lymphoma, multiple myeloma and gastric cancer. On September 2021, the FDA granted accelerated approval to tisotumab vedotin for patients with recurrent or metastatic cervical cancer. Currently, the role of therapy of ADCs on gynecologic tumors was also included in medication regimens. Now more than 30 ADCs targeting for 20 biomarkers are under clinical trials in the field, including monotherapy or combination with others for multiple lines of therapy. Some ADCs have been proved to enhance the antitumor immunity effect on both pre-clinical models and clinical trials. Therefore, combination of ADCs and ICIs are expected in clinical trials. In this review, we discuss current development of ADCs in gynecologic oncology and the combination effects of ICIs and ADCs.

Updates on Therapy for Gynecologic Cancers

Updates on Therapy for Gynecologic Cancers

The Application of Carbon Nanomaterials in Sensing, Imaging, Drug Delivery and Therapy for Gynecologic Cancers: An Overview.

Gynecologic cancers are one of the main health concerns of women throughout the world, and the early diagnosis and effective therapy of gynecologic cancers will be particularly important for the survival of female patients. As a current hotspot, carbon nanomaterials have attracted tremendous interest in tumor theranostics, and their application in gynecologic cancers has also been developed rapidly with great achievements in recent years. This Overview Article summarizes the latest progress in the application of diverse carbon nanomaterials (e.g., graphenes, carbon nanotubes, mesoporous carbon, carbon dots, etc.) and their derivatives in the sensing, imaging, drug delivery, and therapy of different gynecologic cancers. Important research contributions are highlighted in terms of the relationships among the fabrication strategies, architectural features, and action mechanisms for the diagnosis and therapy of gynecologic cancers. The current challenges and future strategies are discussed from the viewpoint of the real clinical application of carbon-based nanomedicines in gynecologic cancers. It is anticipated that this review will attract more attention toward the development and application of carbon nanomaterials for the theranostics of gynecologic cancers.

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis-The Triple Incision Approach.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs’ measures were analyzed by Student’s t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

Sexual health and function among patients receiving systemic therapy for primary gynecologic cancers

ObjectiveSexual dysfunction has been reported after gynecologic cancer treatment but few studies have examined sexual function during treatment. Our objectives were to describe sexual function among women receiving systemic therapy for gynecologic cancers and to compare sexual function between women receiving upfront treatment versus treatment for cancer recurrence. MethodsWe conducted a prospective study of women 18yo and older receiving systemic therapy for gynecologic cancer in the upfront or recurrent setting. Patients receiving radiation were excluded. Participants completed a survey with questions from the Patient Reported Outcome Measurement Information System (PROMIS) SexFS and Female Sexual Function Index (FSFI). Clinical information was collected from chart review. Statistical analysis included t-test, Wilcoxon rank sum test, and Fisher's exact test. ResultsOf 145 patients approached, 100 (69%) enrolled and 97 (67%) completed the survey. Median age was 65yo. Most patients had ovarian cancer (58%), then endometrial cancer (34%) and cervical cancer (8%). Fifty-two (54%) were receiving recurrent treatment and 45 (46%) upfront treatment. Thirty-eight (76%) in the recurrent group and 34 (75%) in the upfront group hadn't been sexually active in the last month (p = 1.0); however, 61 (67%) participants reported a desire for future sexual activity. Of the 31 patients who completed all FSFI questions, the median FSFI score was 24.0 and 21 (68%) had sexual dysfunction. Vaginal dryness was more common among patients receiving recurrent treatment (p = 0.09) while a “health condition” was a more common reason for sexual inactivity in the upfront setting (p = 0.07). ConclusionMany patients receiving systemic therapy for gynecologic cancers are willing to discuss sexual function. Most patients reported sexual dysfunction and weren't currently sexually active. Understanding patients' sexual function concerns will allow providers to intervene.

Clinical Implementation and Initial Experience With a 1.5 Tesla MR-Linac for MR-Guided Radiation Therapy for Gynecologic Cancer: An R-IDEAL Stage 1 and 2a First in Humans Feasibility Study of New Technology Implementation

PurposeMagnetic resonance imaging–guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiation therapy plans. Here, we report our early clinical experience using a MR-linac for adaptive radiation therapy of gynecologic malignancies. Methods and MaterialsTreatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here, we documented the duration of each treatment fraction; set-up variability (assessed by isocenter shifts in each plan) between fractions; and, for quality assurance, calculated the percentage of plans meeting the γ-criterion of 3%/3-mm distance to agreement. Deformable accumulated dose calculations were used to compare accumulated versus planned dose for patient treated with exclusively ATP fractions. ResultsOf the 10 patients treated with 90 fractions on the MR-linac, most received boost doses to recurrence in nodes or isolated tumors. Each treatment fraction lasted a median 32 minutes; fractions were shorter with ATP than with ATS (30 min vs 42 min, P < .0001). The γ criterion for all fraction plans exceeded >90% (median, 99.9%; range, 92.4%-100%; ie, all plans passed quality assurance testing). The average extent of isocenter shift was <0.5 cm in each axis. The accumulated dose to the gross tumor volume was within 5% of the reference plan for all ATP cases. Accumulated doses for lesions in the pelvic periphery were within <1% of the reference plan as opposed to –1.6% to –4.4% for central pelvic tumors. ConclusionsThe MR-linac is a reliable and clinically feasible tool for treating patients with gynecologic cancer.

Changes in the Vaginal Microbiome and Associated Toxicities Following Radiation Therapy for Gynecologic Cancers.

Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.

101: A Single Institution Retrospective Study of Pelvic Insufficiency Fractures Following Curative-Intent Pelvic Intensity-Modulated Radiation Therapy for Gynecologic, Gastrointestinal and Genitourinary Cancers

101: A Single Institution Retrospective Study of Pelvic Insufficiency Fractures Following Curative-Intent Pelvic Intensity-Modulated Radiation Therapy for Gynecologic, Gastrointestinal and Genitourinary Cancers

Deficient Health Care Services as Barriers to Meet Care Needs of Gynecological Cancer Survivors in Indonesia: A Qualitative Inquiry.

This study aimed to gain insight into the unmet care needs and health care service barriers experienced by Indonesian gynecological cancer survivors after cancer therapy. Twenty purposively selected women who had completed gynecological cancer therapy for at least 1 year participated in a descriptive qualitative study. Data were collected through in-depth interviews and thematically analyzed. The analysis constructed two themes and seven subthemes: (a) unmet care needs (subthemes: late side effects; cancer recurrence; stigma of cancer transmission; social-economic concerns), (b) deficient functions of health care services (subthemes: short consultation time; unempathetic health professionals; and inefficient time and cost for the health care services). The gynecological cancer survivors experienced shortages of informational, psychological, and socioeconomic support after cancer therapy because of the deficient quality of the health care services. Nursing interventions could mitigate the unmet care needs of gynecological cancer survivors after cancer therapy through patient-centered care services and multidisciplinary collaboration.

28596 Efficacy of laser CO2 treatment for lymphedema secondary to gynecologic cancer therapy

Genital lymphedema is a debilitating possible side effect of gynecologic and pelvic malignancies. With a prevalence of 2-3 million cases in the US, lymphedema is a common chronic inflammatory condition due to lymphatic insufficiency often occurring secondary to surgery, tumor burden, trauma or radiation. Studies estimate 1 in 5 breast cancer patients will experience chronic upper extremity edema; however, other malignancies are less explored. Genital lymphedema may significantly affect quality of life with sequela of lymphorrhea, swelling, and urinary retention. Suggested first line care is non-surgical management; however, no standard recommendations exist. We present a 62-year-old woman with stage IIB grade 3 cervical cancer presenting to dermatologic surgery for evaluation of chronic vulvar lymphedema after total abdominal hysterectomy with bilateral salpingoopherectomy and lymph node dissection with subsequent chemotherapy and pelvic radiation. She developed painful bilateral lower extremity, anterior pelvis and mons pubis lymphedema within two months of treatment. The patient experienced emotional distress due to seven episodes of cellulitis, admissions to the hospital, impaired ability to exercise and decreased aesthetic satisfaction. After failing traditional management with chronic antibiotic therapy, compression stockings and massage therapy and having been rendered a poor surgical candidate for lymph node transfer, she visited dermatology. Six sessions of fractional CO2 laser [Lumenis Deep Fx Fractional CO2 laser, Coherent USA] therapy have been performed with success in decreasing lymphorrhea, edema, and cellulitis episodes allowing stoppage of prophylactic antibiotics. This case explores and highlights the use of fractional CO2 laser therapy for treatment of lymphedema and its sequela.

Engineered T Cell Therapy for Gynecologic Malignancies: Challenges and Opportunities.

Gynecologic malignancies, mainly including ovarian cancer, cervical cancer and endometrial cancer, are leading causes of death among women worldwide with high incidence and mortality rate. Recently, adoptive T cell therapy (ACT) using engineered T cells redirected by genes which encode for tumor-specific T cell receptors (TCRs) or chimeric antigen receptors (CARs) has demonstrated a delightful potency in B cell lymphoma treatment. Researches impelling ACT to be applied in treating solid tumors like gynecologic tumors are ongoing. This review summarizes the preclinical research and clinical application of engineered T cells therapy for gynecologic cancer in order to arouse new thoughts for remedies of this disease.

Feasibility of a telemedicine lifestyle-based rehabilitation program (HEAL) for gynecologic cancer patients.

e24033 Background: General health related factors such as obesity, unhealthy diets disproportionate with sugary and highly processed foods, inactivity, and smoking have repeatedly been shown to negatively impact survival and quality of life outcomes in cancer survivors. The Healthy Eating Active Lifestyle (HEAL) – GYN “rehabilitation” cancer program was developed to provide intensive group lifestyle training on exercise, nutrition, sleep, social integration, and stress management via a telemedicine platform. The aim of this study was to determine the feasibility of such an intervention and its tolerability, in addition to its impact on short-term quality of life for gynecologic cancer patients. Methods: HEAL – GYN consists of 8 weekly group sessions offering experiential instruction and personalized goal setting for patients with diagnosis of gynecologic cancer. Components are drawn from the tenets of lifestyle medicine. An oncologist certified in lifestyle medicine along with a multidisciplinary rehabilitation team addressed diet, physical activity, strategies for sleep and stress management, smoking cessation, and alcohol intake. The intervention included training to address unmet psychologic, emotional, physical, sexual, social, and spiritual needs common to cancer survivors. American College of Lifestyle Medicine questionnaires were administered, utilizing Likert scales (1-5) in a pre- and post- fashion to assess improvements in physical activity levels, dietary habits, sleep hygiene, and quality of life. Medical records were reviewed including anthropometric data. Results: 26 patients have enrolled thus far, and we report outcomes on the first 20 participants. The mean age was 58.8 years; 22 were Caucasian, and 7 were on maintenance therapies for gynecologic cancers. Average total severity of reported symptoms (scale = 100 points) on a general medical symptom questionnaire (MSQ) decreased by 22% (61 vs 48). Eight patients reported increased perceived levels of health and 6 had stable perception of health. There were also notable improvements from baseline in item assessments of eating behavior (34%), perceived stress (20%), and resilience (21%). Patients also reported a notable trend towards improvement in anxiety (35%) and depression (34%), as well as social integration and connectedness (30%). 100% of participants would “highly recommend the program” and none complained of stress or altered mood associated with online instruction. Conclusions: The telemedicine HEAL – GYN peri-habilitation program is feasible and well tolerated. In addition, the program may improve quality of life and may prevent further decline for those on treatment or maintenance therapy. These preliminary findings support continued investigation of a telemedicine healthy lifestyle peri-habilitative program.

Body Fluid Trend and Prevalence of Lymphedema After Gynecological Cancer Surgery.

Background: This study aimed at understanding the trend in extracellular fluid (ECF) change and estimating the efficacy of the early complex decongestive therapy (CDT) program in terms of prevalence of lower limb lymphedema, as well as at identifying the quality of life (QoL) associated with response to CDT after gynecological cancer therapy. Methods and Results: Thirty-one patients undergoing gynecological cancer treatment were enrolled and randomly assigned to the CDT and control groups. In the CDT group, CDT was started within 2 weeks after surgery for 30 minutes a day, for 2 weeks (5 days per week). The patients' QoL was assessed through the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire; version 3. Inbody S10® (Biospace, Seoul, South Korea) was used to calculate the ECF. The assessment was performed at pre- and post-surgery and at 3, 6, and 12 months after surgery. Statistically significant differences, in favor of the CDT group, were encountered at the 3-month follow-up visit, especially with respect to the QoL score. Regarding the prevalence of lymphedema, no significant difference was observed between groups. The mean value of the impedance ratio was low in the CDT group during the entire 12 month follow-up. Conclusions: The results of the present study show that early CDT had a positive effect on the prevalence of lymphedema and body composition. Long-term follow-up studies with a larger sample size are needed to warrant the time-group effect of early rehabilitation.

Dosimetric predictors of nephrotoxicity in patients receiving extended-field radiation therapy for gynecologic cancer

PurposeWe sought dosimetric predictors of a decreasing estimated glomerular filtration rate (eGFR) in gynecological oncology patients receiving extended-field radiation therapy (EFRT).Materials and methodsBetween July 2012 and April 2020, 98 consecutive cervical or endometrial cancer patients underwent EFRT or whole-pelvis radiation therapy (WPRT) with concurrent cisplatin chemotherapy in our institution. To explore the effect of concurrent cisplatin chemotherapy on renal function, the renal function of the WPRT patients was examined. Of the 98 patients, 34 cervical or endometrial cancer patients underwent EFRT including extended-field intensity-modulated radiation therapy (EF-IMRT) and 64 cervical cancer patients underwent WPRT with cisplatin. Of the 34 EFRT patients, 32 underwent concurrent cisplatin chemotherapy. Excluding patients exhibiting recurrences within 6 months, 31 EFRT patients were analyzed in terms of the dose-volume kidney histograms (the percentages of kidney volumes receiving 12, 16, 20, and 24 Gy) and the post- to pre-treatment eGFR ratios. We calculated Pearson correlation coefficients between the renal dose volume and the percentage eGFR reductions of the 31 EFRT patients, and those treated via EF-IMRT. Renal dose constraint significance was evaluated using the Mann–Whitney U test.ResultsThe eGFR value after WPRT with cisplatin remained largely unchanged for 12 months, unlike that after EFRT. In EFRT patients, a strong correlation was evident between the KV20Gy dose and the post- to pre-treatment eGFR ratio (correlation coefficients − 0.80 for all patients and − 0.74 for EF-IMRT patients). In EF-IMRT patients, the kidney volume receiving 20 Gy tended to correlate negatively with the eGFR reduction. The Mann–Whitney U test showed that patients with KV20Gy values < 10% retained significantly better renal function than did patients with KV20Gy values > 10% (P = 0.002).ConclusionsImposition of a severe kidney dose constraint during EF-IMRT may reduce nephrotic toxicity. Future prospective investigations of kidney-sparing EF-IMRT are required.