Pleasurable and problematic receptive anal intercourse and diseases of the colon, rectum and anus.

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable.

Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus.

PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

Longitudinal assessment of hepatocellular carcinoma response to stereotactic body radiation using gadoxetate-enhanced MRI: A case series.

PURPOSE: To describe the longitudinal response in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) and who underwent liver transplant (LT) using gadoxetate-enhanced MRI. METHODS: Five men (median age 61y, range 57-64y) with 6 HCCs treated with SBRT (median dose 50 Gy) who subsequently underwent LT were included in this retrospective study. Patients underwent gadoxetate-enhanced MRI before and after SBRT over a period of 3-18 months. Response was assessed using RECIST1.1, mRECIST, LI-RADS and image subtraction, by 2 observers in consensus. Percentage of pathologic tumor necrosis was evaluated. RESULTS: LT was performed 278 days (IQR, 148-418d) after completion of SBRT and 48d after the last MRI. Histopathology demonstrated tumor necrosis of 48 ± 42% (range, 10-100%). Mean tumor size at baseline and last post-treatment MRIs pre-LT were 2.6 ± 0.8 cm and 2.4 ± 0.9 cm. Enhancing tumor component size at baseline MRI and last post-treatment MRI pre-LT were 1.6 ± 0.8 cm and 0.9 ± 1.0 cm. Responses assessed at the last LRI pre-LT were: partial response (PR, n = 3), stable disease (SD, n = 3) using RECIST1.1; complete response (CR, n = 2), partial response (PR, n = 2), stable disease (SD, n = 2) using mRECIST; and LR-TR viable (n = 4), LR-TR non-viable (n = 2) using LI-RADS. At the last MRI pre-LT, per-lesion features of arterial phase hyperenhancement (APHE, 4/6), portal venous washout (3/6) and capsule (3/6) were observed. 5/6 lesions displayed a hypointense perilesional halo on hepatobiliary phase with a mean delay of 3.1 months post-SBRT. CONCLUSIONS: This case-series showed decreased size, persistent APHE, and incomplete pathologic necrosis in most HCCs treated with SBRT undergoing transplant.

Clinical and treatment characteristics of secondary bladder malignancies following low dose rate brachytherapy for prostate cancer.

PURPOSE/OBJECTIVES: To characterize the clinical course and prognosis of bladder malignancies associated with prior prostate brachytherapy SUBJECTS/PATIENTS AND METHODS: We queried our institutional database for patients with bladder cancer (BC) diagnosed between January 2005 and April 2019 who had previously undergone low dose rate (LDR) prostate brachytherapy. Patients diagnosed with BC at least 1 year following LDR prostate brachytherapy with or without external beam radiation therapy were included. Clinical and disease-specific characteristics were abstracted from chart review and survival outcomes were estimated using Kaplan-Meier estimates. We compared the pathologic characteristics and prognosis of secondary BCs in our study cohort to those of BCs diagnosed after prostate cancer managed without radiation reported by the Surveillance, Epidemiology, and End Results (SEER) populational database from 2005 to 2018. RESULTS: Three hundred seventy-five patients were identified with combined diagnosis of prostate cancer and BC, 51 of whom met inclusion criteria in the study cohort. Median times from brachytherapy to BC diagnosis for the study and SEER cohort were 9.5 ± 4.5 and 6.3 ± 4.1 years, respectively. Compared to the SEER cohort, significantly greater proportion of BC from the study cohort presented with high-grade (study: 78.4%, SEER: 52.3%, P = 0.0008) and with MIBC (Study BC 35.3%, SEER BC: 17.5%, P = 0.0009). The study and the SEER cohort had similar 5-year overall survival (study: 67.9%, SEER: 58.0%, P = 0.1099), and 5-year cancer-specific survival (study: 81.0%, SEER: 82.8%, P = 0.5559). The 5-year progression-free survival for the study cohort was 43.7% (95% CI: 28.8-57.7). CONCLUSION: Compared to bladder cancers following prostate cancer managed without radiation, bladder malignancies following prostate LDR brachytherapy present with higher grade and are more likely to be muscle invasive. Despite the aggressive presenting features of postprostate brachytherapy BC, there were no differences in overall and cancer-specific survival between the groups.

The Rise of Open Access Journals in Radiation Oncology: Influence on Resident Research, 2015 to 2019.

Purpose: While a rising share of scientific research articles are being published in open access (OA) journals, their impact on resident research in radiation oncology is unknown. Thus, we sought to determine the number, content, and costs of first-author, PubMed-searchable articles radiation oncology residents in the United States (US) published in OA journals in recent years. Methods and Materials: We built a database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019. We then classified each journal in which these articles appeared as either OA or non-OA and obtained the current article-processing charge (APC) for each publication that appeared in an OA journal. Results: The residents in this study published 2637 first-author, PubMed-searchable articles, 555 of which (21.0%) appeared in 138 OA journals. The number of publications in OA journals per resident increased from 0.47 for the class of 2015 to 0.79 for the class of 2019. Publications in OA journals garnered fewer citations than those in non-OA journals (8.9 vs 14.9, P < .01). Furthermore, 90.6% of OA journals levy an APC for original research reports (median, $1896), which is positively correlated with their 2019 impact factor (r = 0.63, P < .01). Aggregate APCs totaled $900,319.21 and appeared to increase over the study period. Conclusions: The number of first-author, PubMed-searchable articles published by graduating US radiation oncology residents in OA journals rose significantly between 2015 and 2019. To maximize the benefits of OA publishing in the future, US radiation oncology residents will need to ensure that they use vetted OA journals to publish their research findings and avoid predatory journals.

Oligoprogression of Solid Tumors on Immune Checkpoint Inhibitors: The Impact of Local Ablative Radiation Therapy.

The breakthrough of a limited number of clones while on immune checkpoint inhibitors (ICIs), known as oligoprogression, has been previously described. The benefit of ablative radiation therapy (RT) directed at these clones, as opposed to changing systemic therapy, is unclear. We analyzed 30 patients with advanced solid tumors, the majority of whom (23/30, 86.7%) had either hepatocellular or urothelial carcinoma, who experienced oligoprogression on ICIs and were referred for RT. In this study, oligoprogression was defined as having experienced progression at three or fewer metastatic sites outside of the brain after achieving at least stable disease on ICIs for a minimum of three months. The median time to oligoprogression was 11.1 months from the initiation of immunotherapy. 24 patients had one oligoprogressive lesion and six had two. The median radiation dose delivered was 4650 cGy in a median of five fractions. The median progression-free survival (PFS) after RT was 7.1 months, and the time to oligoprogression was not a significant predictor of PFS2. 26 patients continued on ICIs after RT. While 17 patients subsequently progressed, 15 did so at three or fewer metastatic sites and could have theoretically stood to benefit from an additional course of salvage RT to further extend the lifespan of their ICIs. Overall survival at 6, 12, and 24 months was 100.0%, 96.3%, and 82.8%, respectively. These results suggest that RT may provide a PFS benefit and extend the lifespan of ICIs in patients who experience oligoprogression. Regardless of PFS, however, overall survival in this population appears to be excellent.

Characterization of rib fracture development following liver directed stereotactic body radiation therapy.

Purpose: Rib fractures are a well-described complication following thoracic stereotactic body radiation therapy (SBRT). However, there are limited data in the setting of liver-directed SBRT. Methods: Patients who underwent liver SBRT from 2014 to 2019 were analyzed. Logistic regression models were used to identify the demographic, clinical, and dosimetric factors associated with the development of rib fractures. Results: Three hundred and forty-three consecutive patients were reviewed with median follow-up of 9.3 months (interquartile range [IQR]: 4.7-17.4 months); 81% of patients had primary liver tumors and 19% had liver metastases. Twenty-one patients (6.2%) developed rib fractures with a median time to diagnosis of 7 months following SBRT (IQR: 5-19 months). Of those patients, 11 experienced concomitant chest wall pain, while 10 patients had an incidental finding of a rib fracture on imaging. On univariate analysis, female gender (odds ratio [OR]: 2.29; p = 0.05), V30 Gy (OR: 1.02; p < 0.001), V40 Gy (OR: 1.08; p < 0.001), maximum chest wall dose (OR: 1.1; p < 0.001), and chest wall D30 cm3 (OR: 1.09; p < 0.001) were associated with an increased probability of developing a rib fracture. On multivariate analysis, maximum chest wall dose (OR: 1.1; p < 0.001) was associated with developing a rib fracture. Receipt of more than one course of SBRT (p = 0.34), left versus right sided lesion (p = 0.69), osteoporosis (p = 0.54), age (p = 0.82), and PTV volume (p = 0.55) were not significant. Conclusions: Rib fractures following liver SBRT were observed in 6.2% of patients with the majority being asymptomatic. To mitigate this risk, clinicians should minimize dose delivery to the chest wall. Female patients may be at increased risk.

Characterization and Prediction of Signal Intensity Changes in Normal Liver Parenchyma on Gadoxetic Acid-enhanced MRI Scans after Liver-directed Radiation Therapy.

Purpose To better characterize and understand the significance of focal liver reaction (FLR) development in a large cohort of patients who underwent gadoxetic acid-enhanced MRI after being treated with radiation therapy (RT) for hepatobiliary tumors. Materials and Methods This retrospective study evaluated 100 patients (median age, 65 years [first and third quartiles, 60-69 years]; 80 men) who underwent RT for hepatocellular carcinoma, bile duct tumors, or liver metastases at Mount Sinai Hospital between March 1, 2018, and February 29, 2020. CT simulation scans were fused to MRI scans obtained 1-6 months and 6-12 months after RT, using the hepatobiliary phase of the MRI. To define FLR volume, two radiation oncologists independently delineated the borders of the hypointensity observed on MRI scans in the liver region where RT was delivered. Biologically effective dose (BED) thresholds for the formation of FLRs were calculated, along with albumin-bilirubin (ALBI) scores and grades, and overall survival. Results Most patients developed FLRs, which decreased in volume over time. Median BED threshold values for FLR development were 63.6 Gy at 1-6 months and 88.7 Gy at 6-12 months. While higher baseline ALBI scores were associated with a lower rate of FLRs, there was a significant association between FLR volume and increase in ALBI score at 1-6 months (P = .048). Twelve- and 24-month survival estimates for the cohort were 81% and 48%, respectively. Histopathologic analysis of seven explanted liver specimens demonstrated findings consistent with radiation-induced liver disease. Conclusion FLRs were a clear measure of liver damage after RT and were associated with the development of liver dysfunction and focal radiation-induced liver disease. Keywords: MRI, Radiation Therapy Supplemental material is available for this article. © RSNA, 2022.

Combination Transarterial Chemoembolization and Stereotactic Body Radiation Therapy for Unresectable Single Large Hepatocellular Carcinoma: Results From a Prospective Phase 2 Trial.

PURPOSE: Patients with hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) early-stage A (BCLC A) not suitable for surgery are first considered for ablation. Nonetheless, objective responses and long-term results for ablation in tumors larger than 3 to 4 cm are suboptimal, creating an unmet clinical need. This phase 2 trial studied combination of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) for BCLC A patients with a solitary HCC from 4 to 7 cm. METHODS AND MATERIALS: Eligible patients were BCLC A, Child-Pugh score ≤7, Eastern Cooperative Oncology Group performance status 0 presenting with a single HCC from 4 to 7 cm not suitable for resection or liver transplantation. Treatment consisted of 2 sessions of drug-eluting bead-TACE within 1 month followed by immediate SBRT. SBRT delivered 35 to 50 Gy in 5 fractions. The primary endpoint was best objective response rate (ORR) by modified Response Evaluation Criteria in Solid Tumours (mRECIST). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and toxic effects. RESULTS: From 2014 to 2020, 32 were enrolled in a single institution with median follow-up of 37 months. Thirty patients had at least 1 posttreatment scan to assess response. ORR in the target lesion was 91%: 63% complete response (CR; n = 20), 28% partial response (n = 9), and 3% progression of disease (n = 1). Median time to CR was 10.1 months. Median OS was not yet reached and median PFS was 35 months. Patients achieving CR had a trend toward improved PFS (P = .09). Toxic effects were low. CONCLUSIONS: This phase 2 trial showed very promising ORR when combining TACE + SBRT in large, unresectable HCC, which translates into excellent OS and PFS. These results provide the rationale for exploring this combination in larger phase 2 and 3 clinical trials and a space where SBRT might offer unique clinical advantage.

Coeliac plexus radiosurgery for pain management in patients with advanced cancer : study protocol for a phase II clinical trial.

INTRODUCTION: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer. METHODS AND ANALYSIS: A single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients" be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association. ETHICS AND DISSEMINATION: Ethic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03323489.

Comparison of Pathologic Complete Response Rates and Oncologic Outcomes in Patients With Surgically Resectable Esophageal Cancer Treated With Neoadjuvant Chemoradiation to 50.4 Gy vs 41.4 Gy.

Background Excellent outcomes and high rates of pathologic complete response (pCR) have been reported in patients with operable esophageal carcinoma using 41.4 Gy of radiation with concurrent carboplatin and paclitaxel. With pCR rates similar to studies using higher doses, it remains unclear whether doses greater than 41.4 Gy result in improved outcomes. This study aims to compare pCR rates and oncologic outcomes in patients treated with neoadjuvant chemoradiation to 50.4 Gy vs 41.4 Gy. Methods We reviewed the charts of patients with operable esophageal carcinoma who were treated with neoadjuvant chemoradiation followed by oncologic resection. Our primary endpoint was the pCR rate. Secondary endpoints were overall survival, progression-free survival (PFS), and toxicity.  Results We identified 43 patients meeting inclusion criteria. Nineteen patients were treated with 41.4 Gy and 24 were treated with 50.4 Gy. Cohorts were well-matched, except for a significantly higher percentage of patients with adenocarcinoma (AC) (89.5% vs 54.2%, p = 0.02), usage of intensity-modulated radiation therapy (IMRT) (100% vs 47.6%; p = 0.002), and usage of carboplatin, plus paclitaxel (100% vs 75%; p = 0.003) in the 41.4 Gy group. The pCR rate for the cohort was 44.2%. No differences in the pCR rate (41.7% vs 47.4%), three-year overall survival (OS) (73.7% vs 77.5%), or three-year PFS (52.8% vs 43.7%) were observed. Late toxicity rates also did not vary significantly (p = 0.2). No grade 4 or 5 events were observed. Conclusion In this small series, there were no differences in the pCR rate, PFS, or OS between those treated with 50.4 Gy and 41.4 Gy. Larger, multi-institutional series are needed to validate these findings.

The Holman Research Pathway in Radiation Oncology: 2010 to 2019.

PURPOSE: There has not been an assessment of the Holman Research Pathway (HRP) in radiation oncology (RO) in nearly 10 years. In this study, we sought to review the demographic characteristics, research productivity during and after residency, job placements, and National Institutes of Health (NIH) grant funding of RO residents who completed the HRP in the modern era. METHODS AND MATERIALS: We created a comprehensive database of RO residents who completed the HRP between 2010 and 2019. Using a variety of data sources, we obtained demographic information, first-author manuscripts published in residency, and first- and last-author manuscripts published in the first 30 months after residency for each resident. In addition, we identified the first and current job and NIH grant funding for each resident. RESULTS: Ninety-seven RO residents who graduated from 50 medical schools and 25 residency programs were included. The majority were male (82.5%), had a PhD (92.8%), and identified as white (64.9%). Collectively, these residents published 212 first-author, PubMed-searchable manuscripts during residency (mean: 2.2) and 142 first- or last-author, PubMed-searchable manuscripts in the first 30 months after completion of residency (mean: 1.5). The number of first-author publications authored by HRP graduates during residency was highly correlated (r = 0.62; P < .01) with the number of first- and last-author publications they authored during the first 30 months after completing residency. Ninety-six of the 97 residents (99.0%) were employed in full-time clinical positions after completing residency. Seventy-six HRP residents (78.4%) obtained an academic position as their first job after residency, only 4 of whom have since left academia, and 20 (20.6%) obtained a nonacademic position. Of the 75 HRP graduates currently employed in an academic position, 39 (52.0%) have their own laboratories. Twenty-three of the 96 HRP residents (24.0%) who secured employment in full-time clinical positions after residency switched jobs over the study period. Lastly, 33 of the 97 HRP residents (34.0%) have thus far received 47 extramural NIH research grants, 15 of which were R-01 grants. CONCLUSIONS: Over the past decade, the HRP has proven successful in training a new cohort of physician investigators in RO. Although productive, HRP residents have had relatively homogenous sex, educational, and racial backgrounds. Ensuring sufficient representation of residents from a variety of backgrounds in the HRP in the future will be crucial.

A first radiotherapy application of functional bulboclitoris anatomy, a novel female sexual organ-at-risk, and organ-sparing feasibility study.

OBJECTIVE: The bulboclitoris (clitoris and vestibular bulbs) is the primary organ responsible for female sexual arousal and orgasm. Effects of radiotherapy on the bulboclitoris are unknown, as its structure/function has yet to be described in radiotherapy, and it overlaps only partially with the external genitalia structure. Our aim was to: describe bulboclitoris structure, function and delineation; compare volume of and dose delivered to the bulboclitoris vs external genitalia; and, compare bulboclitoris-sparing IMRT (BCS-IMRT) to standard IMRT (S-IMRT) to determine reoptimization feasibility. METHODS: Our expert team (anatomist, pelvic radiologist, radiation oncologist) reviewed bulboclitoris anatomy and developed contouring guidance for radiotherapy. 20 female patients with anal cancer treated with chemoradiation were analyzed. Sexual organs at risk (OARs) included the external genitalia and the bulboclitoris. Volumes, dice similarity coefficients (DSCs) and dose received using S-IMRT were compared. Plans were reoptimized using BCS-IMRT. Dose-volume histograms (DVHs) for PTVs and all OARs were compared for BCS-IMRT vs S-IMRT. RESULTS: Bulboclitoris structure, function and delineation are described herein. The bulboclitoris occupies 20cc (IQR:12-24), largely distinct from the external genitalia (DSC <0.05). BCS-IMRT was superior to S-IMRT in reducing the dose to the bulboclitoris, with the greatest reductions in V30 and V40, with no significant changes in dose to other OARs or PTV 1/V95. CONCLUSION: The bulboclitoris can be contoured on planning imaging, largely distinct from the external genitalia. Compared with S-IMRT, BCS-IMRT dramatically reduced dose to the bulboclitoris in anal cancer planning. BCS-IMRT might safely reduce sexual toxicity compared with standard approaches. ADVANCES IN KNOWLEDGE: The structure and function of the bulboclitoris, the critical primary organ responsible for female sexual arousal and orgasm, has yet to be described in the radiotherapy literature. Structure, function and delineation of the bulboclitoris are detailed, delineation and bulboclitoris-sparing IMRT were feasible, and sparing reduces the dose to the bulboclitoris nearly in half in female patients receiving IMRT for anal cancer, warranting further clinical study.