Evidence-Based Management of Hepatocellular Carcinoma: Systematic Review and Meta-analysis of Randomized Controlled Trials (2002-2020).

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized controlled trials (RCTs) have aimed at improving outcomes across disease stages. We aimed to analyze the current evidence and identify potential factors influencing response to therapies. METHODS: We conducted a systematic review of phase III RCTs (2002-2020) across disease stages. A meta-analysis was designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor (TKI)/antiangiogenic or immune checkpoint inhibitor (ICI) therapy. RESULTS: Out of 10,100 studies identified, 76 were phase III RCTs. Among them, a rigorous screening algorithm identified 49 with high quality including a total of 22,113 patients undergoing adjuvant (n = 7) and primary treatment for early (n = 2), intermediate (n = 7), and advanced (first-line, n = 21; second-line, n = 12) stages of disease. Nine of these trials were positive, 6 treatments have been adopted in guidelines (sorafenib [2 RCTs], lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib and ramucirumab), but 2 were not (adjuvant CIK cells and sorafenib plus hepatic arterial infusion with FOLFOX). Meta-analysis of 8 trials including 3739 patients revealed ICI therapy to be significantly more effective in patients with viral hepatitis compared with nonviral-related HCC, whereas no differences related to etiology were observed in patients treated with TKI/anti-vascular endothelial growth factor. CONCLUSIONS: Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results. A meta-analysis of systemic therapies suggests that immunotherapies may be more effective in viral etiologies.

Neoadjuvant therapy for gastrointestinal stromal tumors: A propensity score-weighted analysis.

Retrospective and single-arm prospective studies have reported clinical benefit with neoadjuvant imatinib for GISTs. In the absence of randomized Phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival compared to upfront resection (UR) remains unknown. We identified N = 16 308 patients within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel and colorectum, with or without ≥3 months of NAT. Inverse probability of treatment weighting adjusted for covariable imbalance among treatment groups. We estimated the effect of NAT on overall survival with a weighted time-dependent Cox proportional hazards model, and on 90-day postoperative mortality and R0 resection with weighted logistic regressions. Eight hundred sixty-five (5.3%) patients received NAT compared to 15 443 (94.7%) who underwent UR. Median NAT duration was 6.3 months. 53.7% of NAT patients were male vs 48.6% of UR patients, 67.3% vs 65.1% had primary gastric GIST and 72.8% vs 49.7% were at high risk. NAT patients had larger tumors and higher mitotic index. >3 months of NAT was associated with a significant survival benefit (weighted HR 0.85 [0.80-0.91]). 90-day postoperative mortality rate was 4/865 (0.5%) among NAT patients vs 346/15443 (2.2%). NAT was associated with lower odds of 90-day postoperative mortality. R0 resection rate was not significantly different between groups. In conclusion, despite higher risk features among NAT patients, this analysis suggests that NAT for localized GIST is associated with a modest survival benefit and lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection.

Stage-matched survival differences by ethnicity among gastric cancer patients of Asian ancestry treated in the United States.

BACKGROUND: Differences have been noted in overall survival (OS) in gastric cancer (GC) between trials conducted in Western vs Asian countries. The National Cancer Database (NCDB) reports outcomes and patient/disease variables relevant to OS. METHODS: Using NCDB, we identified 89 558 adult patients with GC diagnosed (2004-2012), where self-reported race/ethnicity was available. Cox proportional hazard model was used to calculate multivariable hazard ratio (HR) of death, adjusting for race/ethnicity, age, gender, insurance, histology, grade, location, stage, and treatment type. RESULTS: After adjustment, Asian patients had improved OS (HR = 0.74, 95% confidence intervals [CI] = 0.71-0.77). There were differences in OS between Asian ethnicities compared with white patients (n = 69 945), notably with Korean (n = 1249, HR = 0.70, 95% CI = 0.64-0.75), Chinese (n = 1271, HR = 0.69, 95% CI = 0.64-0.75), and Indian/Pakistani patients (n = 492, HR = 0.68, 95% CI = 0.61-0.76). Japanese (n = 829, HR = 0.84, 95% CI = 0.77-0.91) and Vietnamese (n = 560, HR = 0.79, 95% CI = 0.71-0.88) OS was also improved (P < 0.0001), while Filipino patients showed no difference (n = 415, HR = 1.00). Black patients had slightly improved OS (n = 13 500, HR = 0.98, 95% CI = 0.95-1.00, P = 0.035). CONCLUSIONS: This analysis supports improved OS in Asian patients independent of stage, treatment, and known patient or disease characteristics in this large US cohort, and is the largest to define OS differences between Asian ethnicities.

Cervical Esophageal Cancers: Challenges and Opportunities.

PURPOSE OF THE REVIEW: Cervical esophageal cancers (CECs) are a rare subset of esophageal cancers that are distinct in their management and outcomes. This review explores current data on the optimal management of this disease. RECENT FINDINGS: While outcomes for CEC have been suboptimal, several strategies have been proven beneficial in recent years. These include selective surgical resection or salvage surgery, chemoradiation (CRT) vs. radiation (RT) alone, dose escalation, IMRT, and induction chemotherapy. The optimal management of CEC to achieve the best oncological outcomes and minimize morbidity appears to be definitive chemoradiation with surgery reserved for selective salvage. While the benefit of dose escalated vs. standard dosing for radiation is unclear, most appear to use doses in excess of 50.4 Gy, even in the United States. IMRT might provide a benefit independent of allowing for dose escalation. Induction chemotherapy might allow for "chemoselection", but the benefit is unclear.

Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.

OBJECTIVE: To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan-Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes. RESULTS: A total of 902 patients were identified, with a median follow-up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P < 0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were reported by patients at any point during treatment follow-up. Analysis of patients who were potent before treatment using actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040). CONCLUSION: Brachytherapy monotherapy results in equal biochemical and distant control in both patients with one and more than one intermediate-risk features. While no significant benefit was shown, we believe that the addition of EBRT may prevent recurrence in patients with multiple intermediate-risk features and should be considered.

A Population-Based Cohort Analysis of Chemoradiation Versus Radiation Alone for Definitive Treatment of Stage I Anal Cancer in Older Patients.

BACKGROUND: Although the benefit of chemoradiation over radiation therapy alone has been shown in randomized trials for stage II to III squamous cell of the anus, this benefit is not clear for patients with stage I cancer. Nevertheless, most societal recommendations endorse chemoradiation for patients with stage I squamous cell carcinoma of the anus despite the lack of proven benefit and potential increase in toxicity. OBJECTIVE: The purpose of this study was to determine whether outcomes are improved with the addition of chemotherapy versus radiation alone for stage I squamous cell carcinoma of the anus. DESIGN: This was a cohort analysis using Surveillance, Epidemiology and End Results registry linked to Medicare from 1996 to 2011. Propensity-score methods were used to control for potential confounding. SETTINGS: This was a population-based study. PATIENTS: Medicare eligible patients (age >65 y or with an eligible disability) with stage I squamous cell carcinoma of the anus treated with either definitive radiation alone or chemoradiation were included. INTERVENTIONS: Radiation or chemoradiation was the intervention. MAIN OUTCOME MEASURES: Overall survival, disease-free survival, cause-specific survival, colostomy-free survival, and acute or late toxicities were measured. RESULTS: A total of 200 patients with squamous cell carcinoma of the anus were identified who received chemoradiation versus 99 treated with lone radiotherapy. Median age was 72 years and did not differ by treatment (p = 0.6). Patients receiving chemoradiation had improved unadjusted overall survival compared with lone radiotherapy, but after adjustment using propensity-score methods there was no difference in overall survival (HR = 0.7 (95% CI, 0.4-1.0)), cause-specific survival (HR = 0.7 (95% CI, 0.3-1.6)), colostomy-free survival (HR = 1.1 (95% CI, 0.5-2.5)), or disease-free survival (HR = 0.9 (95% CI, 0.6-1.4)). Chemoradiation was associated with an increased risk of select early and late toxicities. LIMITATIONS: This is a retrospective series from an anonymous database. The data might not be relevant for younger, healthier patients. CONCLUSIONS: Lone radiation may be associated with adequate oncologic outcomes when used to treat older and sicker patients with stage I anal cancer. Physicians should discuss the potential benefits and harms of adding chemotherapy for the treatment of these patients. See Video Abstract at http://links.lww.com/DCR/A628.

Gastric adenocarcinoma in young adult patients: patterns of care and survival in the United States.

BACKGROUND: Evidence regarding gastric cancer patients < 40 years old is limited. This study examines young adults with gastric adenocarcinoma in the National Cancer Database to describe demographics and treatment practices, and to develop a nomogram to predict survival. METHODS: The database was queried for adult patients diagnosed with gastric adenocarcinoma from 2004 to 2013. Patients were stratified into two age groups: <40 and ≥ 40 years. The database was analyzed to compare demographics, clinical characteristics, and treatments used for each group. Differences in survival were assessed using Kaplan-Meier curves and log-rank test. For adults < 40 years old, an accelerated failure time survival model was fitted for overall survival and a descriptive nomogram was constructed. RESULTS: Of 70,084 patients included, 2615 (4%) were < 40 years old and 67,469 (96%) were ≥ 40 years. Compared to older patients, adults < 40 years old were more likely to be female (46 vs. 35%), non-white (31 vs. 23%), Hispanic (32 vs. 11%), from the northeast (36 vs. 23%), and to present with stage IV disease (59 vs. 42%) and bone metastases (36 vs. 21%; p < 0.001 for all). The nomogram showed clinical stage as the strongest predictor of overall survival, followed by treatment, grade, race, Charlson-Deyo comorbidity score, and sex. CONCLUSIONS: Young adults with gastric adenocarcinoma are more likely to be Hispanic, female, from the northeast, and to present with metastases. Despite these differences, clinical stage, treatment, and tumor grade are most predictive of overall survival for young adult patients.

Tolerability, toxicity, and temporal implications of transoral robotic surgery (TORS) on adjuvant radiation therapy in carcinoma of the head and neck.

OBJECTIVES: Overall treatment package time (from surgery to radiotherapy [RT] completion) > 100 days can portend poor outcomes in head and neck cancer. Faster postoperative recovery seen with transoral robotic surgery may decrease treatment duration and toxicity for adjuvant RT and chemoradiation. METHODS: We retrospectively reviewed all patients treated with transoral robotic surgery (n = 124) and adjuvant RT and chemoradiation (n = 33) at our institution for head and neck cancer from April 2007 to December 2011 to determine treatment duration, acute toxicity, and long-term percutaneous gastric tube rates. RESULTS: The median overall treatment time was 86 days and from surgery to RT start was 41 days; median RT duration was 44 days. No wound breakdown or infection occurred during or after RT. Two-year actuarial locoregional control, distant metastasis-free survival, and overall survival rates were 93%, 96%, and 97%, respectively. CONCLUSIONS: Adjuvant RT after transoral robotic surgery for head and neck cancer can be completed safely and in a timely fashion. Longer follow-up and a larger cohort will be needed to determine if this regimen is more effective than traditional surgery followed by adjuvant RT.

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.

Temporal patterns of selected late toxicities in patients treated with brachytherapy or brachytherapy plus external beam radiation for prostate adenocarcinoma.

UNLABELLED: What's known on the subject? and What does the study add? While the frequencies and severity of late toxicities following prostate brachytherapy are well known, less has been published with regard to time to first onset. Several series with limited median follow-up have published time to onset. An extensive analysis of timing to late toxicity following brachytherapy for cervical cancer has also been published. This study is the largest of its kind with the longest median follow-up to capture very late events. It can provide a basis for physician and patient education about when late toxicities can reasonably be expected to occur. The study also shows that a significant amount of erectile dysfunction might be more age related than radiation induced. OBJECTIVES: • To assess the timing of first onset of late rectal bleeding, late haematuria and erectile dysfunction (ED) following brachytherapy with or without external beam radiation therapy (EBRT) for prostate adenocarcinoma. • To identify treatment factors and patient characteristics that affect the time to first onset. PATIENTS AND METHODS: • In all, 2046 patients were definitively treated for prostate adenocarcinoma with a full (125) I or (103) Pd implant or a partial (103) Pd implant followed by EBRT with 6 years median follow-up (range 2-17 years). • Patients were selected for an event of Radiation Therapy Oncology Group (RTOG) grade 2 or greater rectal bleeding, ≥RTOG grade 2 haematuria, or a drop in the Mount Sinai Erectile Dysfunction Score from potent to impotent (excluding patients who received androgen deprivation therapy). • Life tables were generated to calculate actuarial incidence rates of toxicity. • Wilcoxon rank sum and Cox regression were utilized to identify treatment factors affecting time to onset. RESULTS: • The incidence rate per 1000 patients for 0-2 years, 2-5 years and 5-10 years following radiation for rectal bleeding is 14.3, 15.9 and 6.5, respectively; for haematuria, 14.0, 8.2 and 1.3, respectively; and for ED, 82.4, 48.2 and 42.2, respectively. • Just 5% of rectal bleeding occurs after 5 years from radiation vs 18% of haematuria cases and 22% of ED. • On multivariate analysis, time to first onset of rectal bleeding was affected by the addition of EBRT only whereas the time to onset of haematuria was affected by the biological effective dose of the radiation and the addition of EBRT. • The only factor on multivariate analysis to affect time to onset of ED was the age of the patient at treatment, independent of radiation dose or technique. CONCLUSIONS: • Unique temporality to first onset of selected toxicities was observed in patients after radioactive implant for prostate adenocarcinoma with or without EBRT. • Clinicians and patients should be counselled when to expect late toxicities. • The only factor to affect time to onset of ED is the age of the patient, suggesting possible over-reporting of radiation-induced ED in the light of normal age-related events.

The relative importance of hormonal therapy and biological effective dose in optimizing prostate brachytherapy treatment outcomes.

OBJECTIVES: To compare the relative importance of radiation dose escalation vs androgen deprivation therapy (ADT) in the definitive treatment of prostate adenocarcinoma. PATIENTS AND METHODS: In total, 2427 patients with prostate adenocarcinoma were treated with definitive brachytherapy or brachytherapy with external beam radiation with or without ADT. Over the 20-year period of the present study (median follow-up of 78 months), patients were treated with a range of doses that were converted to the biological effective dose (BED) and/or ADT as the treatment paradigms were optimized. Using univariate and multivariate analysis, the relative impact on the biochemical control and post-treatment prostate biopsy results of BED vs ADT was determined. RESULTS: The 10-year freedom from biochemical failure (FBF) was significantly affected by BED group: ≤150 Gy2 (64%), >150-200 Gy2 (88%), >200-220 Gy2 (89%) and >220 Gy2 (89.5%) (P < 0.001). When stratified into dose groups, ADT improved FPF on multivariate analysis for the BED group (<150 Gy2 , hazard ratio = 0.55; >150-200 Gy2 , hazard ratio = 0.39) but not for the higher BED groups. Among patients receiving ADT, a significant difference in 10-year FBF was seen when stratifying BED into groups ≤150 Gy2 (78%) vs >150 Gy2 (87%) (P = 0.01). On logistic regression, ADT had a significant impact on obtaining a negative biopsy (hazard ratio = 0.21) with BED <200 Gy2 , although there was no difference with BED >200 Gy2 . CONCLUSIONS: When treated with brachytherapy with or without EBT, ADT improves FBF only in the setting of lower doses. The benefit of ADT may be primarily as an enhancer of local control, explaining why high radiation doses can compensate for its absence.

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.

Long-term potency preservation following brachytherapy for prostate cancer.

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Previously, rates of potency preservation with or without external beam radiation and/ or hormone therapy have been published with smaller series and limited follow-up. The study provides greater numbers and longer follow-up giving patients and clinicians a better appreciation of the true potency preservation rates in this population and how various factors such as age, hormone use and external beam affect those rates. OBJECTIVES: • To assess potency preservation in men following brachytherapy for prostate cancer with or without external beam radiation therapy (EBRT) and/or androgen deprivation therapy (ADT). • To evaluate the factors that significantly impact this rate. PATIENTS AND METHODS: • In all, 1063 potent men with T1-T3 prostate cancer were treated from 1990 to 2007 with seed implantation alone ((103) Pd or (125) I) (69.6%) or combined modality treatment consisting of a partial dose (103) Pd implant followed 6-8 weeks later by EBRT (45 Gy, prostate/seminal vesicles only) (30.4%). ADT was used in 49.1% of cases (range 1-27 months). • Patients were required to have a minimum of 2 years follow-up and to be off ADT for a minimum of 1 year. • Erectile function was assessed prior to seed implantation and at each follow-up visit using the physician-assigned Mount Sinai Erectile Function Score (MSEFS): 0, unable to have erections; 1, erections insufficient for intercourse; 2, suboptimal erections but sufficient for intercourse; 3, normal erectile function. Potent was defined as a score of greater than or equal to 2 with or without use of a phosphodiesterase type 5 inhibitor. • The potency rate was calculated using actuarial methods with comparisons tested by log-rank and Cox regression analysis. RESULTS: • The 5-year and 10-year actuarial rate of potency preservation was 68.0% and 57.9%, respectively, at last follow-up. • On multivariate analysis, 5- and 10-year potency was 87.6% (79.5%) for men younger than 60, 68.0% (57.5%) for age 60-70, and 42.2% (31.0%) for men older than 70 (P < 0.001). • Pretreatment MSEFS of 2 had a potency rate of 51.7% (37.2%) vs 74.2% (65.2%) for an MSEFS of 3 (P < 0.001). • There was a 75.8% (62.6%) potency rate without ADT vs 60.0% (53.0%) with ADT (P < 0.001). • Five-year potency was 76.4% for implant alone, 71.0% for implant with EBRT, 62.2% for implant with ADT, and 57.9% for implant with EBRT and ADT (P < 0.001). CONCLUSION: • Increasing initial age at implant, diminished pretreatment erectile function and the use of combination therapy with EBRT and/or ADT significantly increases erectile dysfunction following brachytherapy.

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.

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.