Real-world experience managing unresectable or metastatic small cell carcinoma of the prostate.

INTRODUCTION: Unresectable and metastatic small cell carcinoma of the prostate (SCPC) is a rare and aggressive disease that is under-represented in clinical trials. We carried out a retrospective chart review of metastatic or unresectable SCPC patients at British Columbia (BC) Cancer centers, studying diagnosis and treatment patterns. METHODS: Drug-dispensing records from the six BC Cancer centers were obtained from 2002-2017. For each patient, information was collected on baseline information prior to therapy and for each line of treatment. Treatments at each line were compared regarding time to progression and overall survival by Kaplan-Meier curves. RESULTS: Forty-one patients received treatment; 65.6% had metastatic disease and 61% had pure small cell carcinoma. Median time from treatment to death was 10 months (95% confidence interval [CI] 6-16). Patients with initially prostate-confined disease had a better median overall survival (mOS) of 21 months (95% CI 13-34) compared to those with initially locally advanced (mOS 19 months, 95% CI 5-37) and metastatic disease (mOS 8 months, 95% CI 6-10) (log-rank p=0.0364). All patients received either cisplatin- or carboplatin-based combination chemotherapy as the first-line treatment and 36.7% received second-line therapy. Time to second-line therapy was eight months for those who presented with metastatic SCPC, compared to 13 months for those with initial non-metastatic SCPC. CONCLUSIONS: This single-province, multi-institution cohort reports data on unresectable and metastatic SCPC and highlights the poor prognosis of this rare disease entity.

Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals.

PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment-related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.

Exercise for individuals with bone metastases: A systematic review.

BACKGROUND: Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases. METHODS: MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched to July 16, 2020. RESULTS: A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n = 4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n = 16, 94%) and were delivered by qualified exercise professionals (n = 13, 76%). CONCLUSIONS: Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction.

The effects of adiposity, muscular strength, cardiorespiratory fitness, and fatigue on gait biomechanics in overweight and obese children.

BACKGROUND: Obesity rates continue to increase in the child population. Muscular strength, cardiorespiratory fitness, and fatigue can potentially affect joint stresses in obese children. The purposes are to examine: (1) the relationship between cardiorespiratory fitness and the change in joint stress pre- to post-fatigue; (2) the predictive value of fitness, adiposity, and muscular strength on joint stresses in fatigued and non-fatigued states; and, (3) the relationships between % body fat from skinfold and air displacement plethysmography. METHODS: Twenty-seven children, with body mass index above the 85th percentile for their age participated in this study. Lower limb joint moments were recorded before and after a fatiguing Progressive Aerobic Cardiovascular Endurance Run protocol. Linear regression was used to assess the relationship between (1) fitness and change in joint stress pre- to post-fatigue, and (2) measures of %body fat using skinfold and plethysmography. Furthermore, Bland-Altman analysis quantified the agreement between measured adiposity using the two methods. FINDINGS: The strongest relationship was observed between fitness and the change in the knee extensor moment pre- to post-fatigue (R2 = 0.24). Regardless of fatigue state, adiposity and strength were identified as the strongest predictors of joint moments. Skinfold estimates were moderately predictive (R2 = 0.56) of %body fat from air displacement plethysmography, and these two measures demonstrated instrument agreement with no proportional bias. INTERPRETATION: Fitness level is not related to changes in biomechanics pre- to post-fatigue in overweight and obese children. Adiposity and lower extremity strength most strongly influenced joint moments in the frontal and sagittal planes.

Impact of a global radiation oncology scholarship for trainees: An evaluation of early outcomes.

Global Oncology capacity in Radiation Oncology (RO) needs development. We report on early outcomes of a Canadian Global Oncology elective scholarship program for trainees (2014-2019). The number of global oncology electives increased. Academic deliverables and collaborations were observed. There was evidence of personal and professional development.

Maximizing rectal dose sparing with hydrogel: A retrospective planning study.

External beam radiation therapy for prostate cancer can result in urinary, sexual, and rectal side effects, often impairing quality of life. A polyethylene glycol-based product, SpaceOAR© hydrogel (SOH), implanted into the connective tissue between the prostate gland and rectum can significantly reduce the dose received by the rectum and hence risk of rectal toxicity. The optimal way to manage the hydrogel and rectal structures for plan optimization is therefore of interest. In 13 patients, computerized tomography (CT) scans were taken pre- and post-SpaceOAR© implant. A prescription of 60 Gy in 20 fractions was planned on both scans. Six treatment plans were produced per anonymized dataset using either a structure of rectum plus the hydrogel, termed composite rectum wall (CRW), or rectal wall (RW) as an inverse optimization structure and intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) as a treatment technique. Dose-volume histogram metrics were compared between plans to determine which optimization structure and treatment technique offered the maximum rectal dose sparing. RW structures offered a statistically significant decrease in rectal dose over CRW structures, whereas the treatment technique (IMRT vs VMAT) did not significantly affect the rectal dose. There was improvement seen in bladder and penile bulb dose when VMAT was used as a treatment technique. Overall, treatment plans using the RW optimization structure offered the lowest rectal dose while VMAT treatment technique offered the lowest bladder and penile bulb dose.

Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma.

PURPOSE: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma. METHODS AND MATERIALS: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours. RESULTS: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer. CONCLUSIONS: These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.

Intrafractional organs movement in three-dimensional image-guided adaptive pulsed-dose-rate cervical cancer brachytherapy: assessment and dosimetric impact.

PURPOSE: To prospectively evaluate the intrafractional movements of organs at risk (OARs) and their dosimetric impact during the delivery of pulsed-dose-rate brachytherapy in cervical cancer. PATIENTS AND METHODS: An MRI on Day 1 was used for treatment planning in 19 patients. CT scans were acquired at Days 1, 2, and 3 with delineation of the OARs. The MRI plan was transferred to each CT. The intersection volume between the 10 Gy isodose and the OARs were monitored, reflecting movement. Lower dose evaluated in the maximally exposed 0.1 cm(3) of an organ and lower dose evaluated in the maximally exposed 2 cm(3) of an organ (D(2cm3)) were evaluated on each CT and compared. Results were averaged considering that each CT reflected one-third of the treatment course to evaluate the delivered dose. RESULTS: No major movements of the sigmoid and bladder were observed, whereas the rectum got significantly closer to the implant at Day 2. The consequence was an increase of 6% ± 5.3 (3.7 Gy, α/ß = 3 Gy) of the delivered D(2cm3) from the planned dose, in contrast to 0.2% ± 6.1 for the bladder and 1.1% ± 6.4 for the sigmoid. The increase of the D(2cm3) of the rectum was reported in 17 patients, ranging from 0.4 to 9.4 Gy, leading to a 10.5% overcoming of the dose constraint (75 Gy). Similar tendencies were reported for lower dose evaluated in the maximally exposed 0.1 cm(3) of an organ. CONCLUSIONS: A significant systematic variation was observed for the rectum (+3.7 Gy). As significant random variations were observed, caution should be exercised when the planned D(2cm3) is close to the dose constraints.

Brachytherapy in children with rhabdomyosarcomas of the nasolabial fold.

BACKGROUND: Rhabdomyosarcomas (RMS) of the nasolabial fold can be difficult to manage surgically due to functional and cosmetic limitations. Therefore, brachytherapy (BT) has been proposed to improve local control while limiting the volume of irradiation as well as the extent of the surgical excision. MATERIALS AND METHODS: Sixteen pediatric cases with RMS of the nasolabial fold treated from 1971 to 2005 were retrospectively reviewed. RESULTS: Median follow-up was 4.4 years (1.7-33). Half of the patients were male and their age at diagnosis ranged from 4 months to 13.5 years. Histological subtypes included 10 embryonal and 6 alveolar RMS. Initial treatment consisted of induction multi-agent chemotherapy in all cases. In 12 patients, BT was combined with local excision (4 complete resections, 1 with macroscopic residual disease, and 7 with microscopic disease). Low dose-rate brachytherapy was performed in all cases according to the Paris system, using plastic catheters implanted per-operatively. The doses delivered ranged from 50 to 70 Gy, depending on chemotherapy response, and surgical margin status. 10 patients relapsed: 4 local, 6 regional, and 2 metastatic failures were reported. The median time to relapse was 6.5 months. At the time of analysis eight patients were alive and four had died. Four cases, under palliative care at last check-up, were lost to follow-up. CONCLUSION: BT provided an acceptable local control rate, but the poor regional control of these cases may suggest a need for more aggressive management of cervical regional lymph node regions in RMS of the nasolabial fold.

Adaptive 3D image-guided brachytherapy: a strong argument in the debate on systematic radical hysterectomy for locally advanced cervical cancer.

PURPOSE: To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT). MATERIALS AND METHODS: Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment. RESULTS: Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5-79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005). CONCLUSION: IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.

Outcomes of node-negative breast cancer 5 centimeters and larger treated with and without postmastectomy radiotherapy.

PURPOSE: The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for the rare presentation of pT3pN0cM0 breast cancer. The present analysis examined locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) in pT2 = 5.0-cm and pT3 >5.0-cm tumors treated with mastectomy, stratified by PMRT use. MATERIALS AND METHODS: Between January 1, 1989 and December 31, 2000, the British Columbia provincial database yielded 100 node-negative patients with tumors ≥ 5 cm of 19,846 nonmetastatic breast cancer patients (0.5%). Of these 100 patients, 44 (44%) had received adjuvant PMRT. RESULTS: The PMRT group contained significantly more pT3 >5-cm cases (p = 0.001) and margin-positive cases (p = .03). With a median follow-up of 10 years, the cumulative 10-year LRR rate was 2.3% (95% confidence interval, 0.2-10.5) in the PMRT group vs. 8.9% (95% confidence interval, 3.2-18.2) in the no-PMRT group (p = .2). Regarding LRR in the no-PMRT group, all patients had Grade 3 histologic features (LRR 17%, 5 of 29) and had not received hormonal therapy (LRR 15%, 5 of 34). The 10-year breast cancer-specific survival rate was 85.8% (95% confidence interval 71.0-93.4) in the PMRT group vs. 74.6% (95% confidence interval 59.9-84.5) in the no-PMRT group (p = .2). On multivariate analysis, adjusted for the prognostic and predictive variables, PMRT did not significantly improve the LRR or breast cancer-specific survival rates. CONCLUSION: The present study demonstrated a low LRR rate for node-negative breast cancer ≥ 5 cm. Our results indicate that PMRT should be considered for Grade 3 histologic features and patients not undergoing hormonal therapy.