Skin/mucosa avoidance radiotherapy (SMART) versus conventional volumetric arc-based radiotherapy (VMAT) for the treatment of head and neck cancer: Dosimetric feasibility study.

BACKGROUND: Intensity modulated radiotherapy (IMRT) for head and neck cancer has led to a reduction in radiotherapy doses to normal tissues, like the salivary glands, while maintaining high rates of local control. Oral mucosal and skin toxicity is still a major source of treatment-related morbidity, occurring in most patients. PURPOSE: We conducted a dosimetric feasibility study with the goal of creating a methodology that could theoretically reduce the dose of radiation to skin and oral mucosa, while maintaining comparable avoidance of other organs at risk, and planning target volume (PTV) coverage. METHODS: The clinical plans of patients treated previously were replanned using coplanar VMAT arcs on a TrueBeam STx using the photon optimizer (PO) version 15.6 and the Acuros XB dose calculation algorithm. Comparisons were made between three methodologies: "Conventional," "Skin Sparing" and a skin/mucosa avoiding ("SMART") technique, with dose metrics being compared using analysis of variance, with a Bonferroni correction to account for multiple pairwise comparisons. The maximum grade of mucositis and radiation dermatitis during treatment was correlated to different dose-volume metrics to predict what could be clinically meaningful. RESULTS: Sixteen patients met the study criteria and were replanned using the skin sparing and SMART techniques. Maximum doses to the skin sparing structure were reduced from 64.2 Gy to 56.6 and 55.9 Gy, in the skin sparing and SMART plans (p < 0.0001), and mean doses reduced from 26.7 Gy to 20.0 and 20.2 Gy, respectively (p < 0.0001). Maximum doses to the oral cavity structure were not reduced by either technique, however mean dose to the oral cavity structure was reduced from 39.03 Gy to 33.5 Gy by the SMART technique (p < 0.0001). There was a slight reduction in PTV_High coverage by the V95% in the SMART plans (99.52% vs. 98.79%, p = 0.0073), and a similar slight reduction in PTV_Low coverage by the V95% by both the skin sparing and SMART plans (99.74% vs. 97.89% vs. 97.42%, p < 0.0001). Maximum doses to organs at risk were not statistically different between techniques. Dose to oral cavity and maximum grade experienced during radiotherapy correlated. The Spearman correlation coefficient for dose to 20%, 50%, and 80% of the volume of oral cavity was 0.5 (p = 0.048), 0.64 (p = 0.007), and 0.62 (p = 0.010), respectively. Skin toxicity grade was only found to be correlated with the D20% of the skin sparing structure (Spearman correlation coefficient of 0.58, p = 0.0177). CONCLUSION: The SMART technique appears to be able to reduce maximum and mean skin dose, as well as mean oral cavity doses, while only slightly reducing PTV coverage, with acceptable OAR doses. We feel the improvements warrant investigation in a clinical trial.

Radiation and/or endocrine therapy? Recurrence and survival outcomes in women over 70 with early breast cancer after breast-conserving surgery.

PURPOSE: Women over 70 with early breast cancer treated with breast-conserving surgery are typically offered adjuvant endocrine and radiation therapy. Prior studies have supported the omission of adjuvant radiation in this low-risk population. We sought to compare the effect of adjuvant treatment with endocrine therapy alone, radiation therapy alone or both versus no adjuvant treatment on local control and survival in this population. METHODS: Data were extracted on 1363 breast cancer patients over the age of 70 treated with a breast-conserving surgery from 2003 until 2018. 460 patients met inclusion criteria of pT1N0, invasive disease with negative margins and not treated with chemotherapy. The primary outcome of this population-based study was local recurrence-free survival at 5 and 10 years. RESULTS: Patients receiving no adjuvant therapy had worse local recurrence-free, loco-regional recurrence-free and disease-free survival than patients receiving at least one form of adjuvant therapy (p < 0.05). 5-year local recurrence rates were 0.8% in patients receiving both endocrine and radiation therapy, 1.5% in those receiving radiation alone, 4.2% in those receiving endocrine therapy alone and 12% in those receiving no adjuvant therapy. CONCLUSIONS: This study supports the benefit of some form of adjuvant therapy (radiation alone, endocrine therapy alone or both) in low-risk breast cancer patients over 70. Receiving no adjuvant therapy is associated with poorer outcomes. Many of these patients are candidates for Accelerated Partial Breast Irradiation which can be completed in less than a week. These patients should be offered radiation therapy, endocrine therapy or both.

Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial.

BACKGROUND: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials. METHODS: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. DISCUSSION: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03862911. Date of registration: March 5, 2019.

Letter to the editor: Reply to Ali et al.

This is a response to the letter to the editor from Dr. Ali et al. from Aga Khan University, Karachi, Pakistan.

Six-Month Prostate Cancer Empowerment Program (PC-PEP) Improves Urinary Function: A Randomized Trial.

Purpose: This is a secondary analysis examining a six-month home-based Prostate Cancer-Patient Empowerment Program (PC-PEP) on patient-reported urinary, bowel, sexual, and hormonal function in men with curative prostate cancer (PC) against standard of care. Methods: In a crossover clinical trial, 128 men scheduled for PC surgery (n = 62) or radiotherapy with/without hormones (n = 66) were randomized to PC-PEP (n = 66) or waitlist-control and received the standard of care for 6 months, and then PC-PEP to the end of the year. PC-PEP included daily emails with video instructions, aerobic and strength training, dietary guidance, stress management, and social support, with an initial PFMT nurse consultation. Over 6 months, participants in the PC-PEP received optional text alerts (up to three times daily) reminding them to follow the PFMT video program, encompassing relaxation, quick-twitch, and endurance exercises; compliance was assessed weekly. Participants completed baseline, 6, and 12-month International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Results: At 6 months, men in the PC-PEP reported improved urinary bother (IPSS, p = 0.004), continence (EPIC, p < 0.001), and irritation/obstruction function (p = 0.008) compared to controls, with sustained urinary continence benefits at 12 months (p = 0.002). Surgery patients in the waitlist-control group had 3.5 (95% CI: 1.2, 10, p = 0.024) times and 2.3 (95% CI: 0.82, 6.7, p = 0.11) times higher odds of moderate to severe urinary problems compared to PC-PEP at 6 and 12 months, respectively. Conclusions: PC-PEP significantly improves lower urinary tract symptoms, affirming its suitability for clinical integration alongside established mental health benefits in men with curative prostate cancer.

Testosterone recovery after androgen deprivation therapy in localised prostate cancer: Long-term data from two randomised trials.

BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.

Mediating Effects of Self-Efficacy and Illness Perceptions on Mental Health in Men with Localized Prostate Cancer: A Secondary Analysis of the Prostate Cancer Patient Empowerment Program (PC-PEP) Randomized Controlled Trial.

Understanding how interventions reduce psychological distress in patients with prostate cancer is crucial for improving patient care. This study examined the roles of self-efficacy, illness perceptions, and heart rhythm coherence in mediating the effects of the Prostate Cancer Patient Empowerment Program (PC-PEP) on psychological distress compared to standard care. In a randomized controlled trial, 128 patients were assigned to either the PC-PEP intervention or standard care. The PC-PEP, a six-month program emphasizing daily healthy living habits, included relaxation and stress management, diet, exercise, pelvic floor muscle exercises, and strategies to improve relationships and intimacy, with daily activities supported by online resources and live sessions. Participants in the intervention group showed significant improvements in self-efficacy and specific illness perceptions, such as personal control and emotional response, compared to the control group. These factors mediated the relationship between the intervention and its psychological benefits, with self-efficacy accounting for 52% of the reduction in psychological distress. No significant differences in heart rhythm coherence were observed. This study highlights the critical role of self-efficacy and illness perceptions in enhancing psychological health in prostate cancer patients through the PC-PEP. The results underscore this program's effectiveness and the key mechanisms through which it operates. Given the high rates of distress among men undergoing prostate cancer treatments, these findings emphasize the importance of integrating the PC-PEP into clinical practice. The implementation of the PC-PEP in clinical settings can provide a structured approach to reducing psychological distress and improving overall patient well-being.

PC-PEP, a Comprehensive Daily Six-Month Home-Based Patient Empowerment Program Leads to Weight Loss in Men with Prostate Cancer: A Secondary Analysis of a Clinical Trial.

Background: The Prostate Cancer-Patient Empowerment Program (PC-PEP) is a six-month daily home-based program shown to improve mental health and urinary function. This secondary analysis explores weight loss in male PC-PEP participants. Methods: In a randomized clinical trial with 128 men undergoing curative prostate cancer (PC) treatment, 66 received 'early' PC-PEP, while 62 were assigned to the 'late' waitlist-control group, receiving 6 months of standard-of-care treatment followed by 6 months of PC-PEP. PC-PEP comprised 182 daily emails with video-based exercise and dietary (predominantly plant-based) education, live online events, and 30 min strength training routines (using body weight and elastic bands). Weight and height data were collected via online surveys (baseline, 6 months, and 12 months) including medical chart reviews. Adherence was tracked weekly. Results: No attrition or adverse events were reported. At 6 months, the early PC-PEP group experienced significant weight loss, averaging 2.7 kg (p < 0.001) compared to the waitlist-control group. Weight loss was noted in the late intervention group of PC-PEP, albeit less pronounced than in the early group. Early PC-PEP surgery patients lost on average 1.4 kg (SE = 0.65) from the trial's start to surgery day. High adherence to exercise and dietary recommendations was noted. Conclusions: PC-PEP led to significant weight loss in men undergoing curative prostate cancer treatment compared to standard-of-care.

A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial.

BACKGROUND: Although survival rates for newly diagnosed prostate cancer patients are very high, most of them will likely suffer significant treatment-related side effects, depression, or anxiety, affecting their quality of life. OBJECTIVE: The aim of this study was to examine the effects of a 6-mo online home-based physical, mental, and social support intervention, the Prostate Cancer Patient Empowerment Program (PC-PEP), on preventing psychological distress among men undergoing curative prostate cancer treatment. DESIGN, SETTING, AND PARTICIPANTS: In a crossover randomized clinical trial of 128 men aged 50-82 yr scheduled for curative prostate cancer surgery or radiotherapy (± hormone treatment), 66 received the 6-mo PC-PEP intervention and 62 were randomized to a waitlist-control arm and received the standard of care for 6 mo, and then PC-PEP to the end of the year. The PC-PEP intervention consisted of daily e-mails with video instructions providing education, patient activation, and empowerment on healthy living including physical and mental health, dietary recommendations, social support, physical and pelvic floor fitness, stress reduction using a biofeedback device, social connection and intimacy, and social support. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was nonspecific psychological distress (clinical cutoff ≥20) measured at baseline, and at 6 and 12 mo using the Kessler Psychological Distress Scale (K10). RESULTS AND LIMITATIONS: At 6 mo, patients in the waitlist-control group had 3.59 (95% confidence interval: 1.12-11.51) times higher odds for nonspecific psychological distress and need for psychological treatment than men who received the PC-PEP intervention. At 12 mo, the wait-list control group that received the intervention at 6 mo had higher psychological distress than the early group. CONCLUSIONS: PC-PEP delivered early following diagnosis significantly prevented the burden of psychological distress in men undergoing curative prostate cancer treatment compared with standard of care, or late (6 mo later) intervention. PATIENT SUMMARY: In this report, we looked at the effectiveness of a program (Prostate Cancer Patient Empowerment Program: PC-PEP) developed with patients' engagement on the mental distress of patients awaiting curative treatment for their prostate cancer. The PC-PEP program lasted for 6 mo, and it prescribed, described, and demonstrated daily aerobic and strength training, kegels (pelvic floor training to help with urinary and sexual function), dietary changes that have been shown to be helpful in the prevention of prostate cancer and prostate cancer progression, stress reduction using a biofeedback device, as well as social and emotional support. All patients in the PC-PEP program were invited to a monthly video conference with the leads of the program who appeared in the 6 mo of daily videos prescribing the activities the patients were asked to watch and follow. The leads were a prostate cancer oncologist and a scientist in prostate cancer quality of life research. Half of the patients in this study received PC-PEP daily for the first 6 mo and were re-assessed at the end of the year. The other half received standard of care for 6 month and then received the intervention to the end of the year. The results of the study show that, at 6 mo, this intervention was effective at reducing the mental distress that accompanies a prostate cancer diagnosis and treatment compared with the standard of care. Mental distress was significantly reduced when the intervention was received early, compared with that received late (6 mo after scheduled curative treatment). We conclude that multi-faceted patient education and empowerment programming of this kind that is developed with patient engagement from the start is crucial to the care of patients diagnosed with prostate cancer and should be implemented in the standard of care. While treatment for prostate cancer is highly successful, side effects that accompany most treatments significantly affect the quality of life of patients. Here, we describe PC-PEP, a patient education and activation program that is cost effective, highly enforced by patients, and successful at reducing the impact of prostate cancer active treatment-related side effects on their psychological state. To learn more about this project, please visit www.pcpep.org. The program is now being tested in a phase 4 implementation trial throughout Canada and internationally (New Zealand), and is being expanded and tested for other types of cancer.

The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Assessing the Efficacy of a 28-Day Comprehensive Online Prostate Cancer Patient Empowerment Program (PC-PEP) in Facilitating Engagement of Prostate Cancer Patients in Their Survivorship Care: A Qualitative Study.

A 28-day Prostate Cancer-Patient Empowerment Program (PC-PEP) developed through patient engagement was successful at promoting mental and physical health. Thirty prostate cancer patients from Halifax, Canada participated in the 28-day PC-PEP intervention in early 2019. PC-PEP encompassed daily patient education and empowerment videos, prescribed physical activities (including pelvic floor exercises), a mostly plant-based diet, stress reduction techniques, intimacy education, social connection, and support. Quantitative exit surveys and semi-structured interviews (conducted in focus groups of ten) were used to assess perceived factors that facilitated or impeded adherence to the program. The program received high praise from the patients and was deemed extremely useful by the participating men, who rated it 9 out of 10. Patients expressed that the multifaceted, online, home-based nature of the program helped them adhere to it better than they would have had to a single or less comprehensive intervention. Feedback from the participants indicated that the program, when viewed as a whole, was perceived as greater than the sum of its individual parts. Furthermore, the program addressed various issues, including emotional vulnerability and distress, physical fitness, urinary incontinence, challenges in expressing emotions, perceived lack of control over healthcare decisions, emotional fragility, and hesitancy to discuss prostate cancer-related matters in social settings. Patients highly (9.6/10) endorsed integrating the program into the standard care regimen from the very beginning of diagnosis. However, challenges such as work commitments were noted. Patients' high endorsement of PC-PEP suggests that its implementation into the standard of care from day one of diagnosis may be warranted.

Estimation of Annual Secondary Lung Cancer Deaths Using Various Adjuvant Breast Radiotherapy Techniques for Early-Stage Cancers.

PURPOSE: Secondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques. PATIENTS AND METHODS: The SEER database was used to extract breast patient age, stage survival, and radiotherapy utilization over time and per stage and to assess the factors associated with increased SLC risk with a multivariable competing risk Cox model. The number of SLC was calculated using the BEIR model modified with patient survival, age, and use of RT from the SEER database. Stage distribution and number of new breast cancer cases were obtained from the NAACCR. Mean lung dose for various irradiation techniques was obtained from measurement or literature. RESULTS: Out of the 765,697 non-metastatic breast cancers in the SEER database from 1988 to 2012, 49.8% received RT. RT significantly increased the SLC risk for longer follow-up (HR=1.58), early stage including DCIS, stage I and IIA (HR = 1.11), and younger age (HR=1.061) (all p<0.001). More advanced stages did not have significantly increased risk. In 2019, 104,743 early-stage breast patients received radiotherapy, and an estimated 3,413 will develop SLC (3.25%) leading to an excess of 2,900 deaths (2.77%). VMAT would reduce this mortality by 9.9%, hypofractionation 26 Gy in five fractions by 38.8%, a prone technique by 70.3%, 3D-CRT APBI by 43.3%, HDR brachytherapy by 71.1%, LDR by 80.7%, and robotic 4π APBI by 85.2%. CONCLUSIONS: SLC after breast RT remains a clinically significant issue for early-stage breast cancers. This mortality could be significantly reduced using a prone technique or APBI.

Personality Traits and Urinary Symptoms Are Associated with Mental Health Distress in Patients with a Diagnosis of Prostate Cancer.

OBJECTIVE: With a prolonged natural history compared with many other cancers, prostate cancer patients have high rates of mental illness over the duration of their treatment. Here, we examine the relationship between personality and mental health distress in a sample of prostate cancer patients. METHODS: This study was conducted in the Canadian Maritime provinces, where a cohort of 189 men with prostate cancer were invited to complete a quality-of-life online survey between May 2017 and December 2019. The presence or absence of screening positive for mental health illness was the primary outcome and was assessed using Kessler's 10-item scale (K10). Urinary symptoms were assessed using the International Prostate Symptom Score (IPSS). The ten-item personality inventory (TIPI) assessed extraversion, agreeableness, conscientiousness, emotional stability (or neuroticism), and openness to experiences. A multivariate logistic regression model was created to examine the association between personality, urinary symptoms, and mental health distress, while controlling for time from diagnosis, treatment type, age, and multimorbidity. RESULTS: Screening positive for mental illness (18.0%) was associated with personality traits of low levels of emotional stability (OR = 0.07, 95% CI: 0.03-0.20) and moderate to severe urinary problems (OR = 5.21, 95% CI: 1.94-14.05)). There was no identified association between treatment received for prostate cancer and personality type. CONCLUSION: Screening for mental health illness in this population may help reduce morbidity associated with cancer treatment, as well as identify patients who may be at risk of mental health distress and could benefit from individualized mental health support services. These findings suggest that multidisciplinary care is essential for the management of these patients.

Optimizing Treatment in Intermediate-Risk Prostate Cancer: Secondary Analysis of a Randomized Phase 3 Trial.

PURPOSE: To identify patients with intermediate-risk prostate cancer (IRPC) benefiting from de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiation therapy (DERT), we performed a secondary analysis of a phase 3 trial by measuring biochemical failure (BF), distant metastases, prostate cancer-specific mortality, overall survival (OS), and distant metastases-free survival (DMFS) rates according to prognostic intermediate risk factors (IRF). METHODS AND MATERIALS: The initial trial randomized 600 patients with IRPC to a 3-arm trial with 200 patients per arm, consisting of 6 months of ADT plus 70 Gy radiation therapy (ADT + RT70) versus ADT plus a DERT of 76 Gy (ADT + DERT76) versus DERT of 76 Gy alone (DERT76). We performed an analysis based on IRF: clinical stage, prostate-specific antigen level, Gleason score, percentage of positive biopsy cores (PBC) ≥50%, and Gleason pattern. Patients were allocated to 2 groups: favorable intermediate risk (FIR), defined as patients with only 1 IRF without Gleason pattern 4 + 3 or PBC ≥50%; and unfavorable intermediate risk (UIR), defined as all other patients. BF, distant metastases, prostate cancer-specific mortality, OS, and DMFS were compared between FIR and UIR. RESULTS: The median follow-up was 11.3 years (interquartile range, 10.9-11.7). In the FIR cohort, BF and OS were not significantly different between arms. UIR patients had significantly worse DMFS (hazard ratio [95% confidence interval], 1.61 [1.20-2.15]; P = .026) and OS (1.51 [1.12-2.04]; P = .0495) and a nonsignificant higher cumulative incidence of BF rate (1.55 [0.98-2.47]; P = .08). In UIR patients, a significant improvement in BF was seen in the arms receiving ADT compared to DERT76 alone. On multivariable analysis, Gleason pattern 4 + 3 and prostate-specific antigen >10 ng/mL independently affected BF and OS, regardless of the treatment arm. CONCLUSIONS: In IRPC, therapeutic optimization appears possible. To avoid ADT side effects, DERT76 alone appears sufficient in patients harboring only 1 risk factor without Gleason pattern 4 + 3 and PBC ≥50% (FIR). All other UIR patients seem to benefit from ADT + DERT76.

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial.

BACKGROUND: The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone. METHODS: From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. FINDINGS: With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity. INTERPRETATION: In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.

Sequence Inversion to Facilitate Concurrent Radiotherapy and Systemic Therapy. A Proof of Principle Study in the Setting of a Phase II Randomized Trial in Prostate Cancer.

Background: Concomitant chemo-radiation for pelvic cancers remains challenging to be delivered at full doses. We hypothesized that fewer delays in chemotherapy would occur if the sequence of radiotherapy would be reversed, starting with the boost volume followed by the elective nodal volume. We report the result of a Phase II randomized study for high risk prostate cancer. Patients and Method: The study was a double-blinded phase II randomized trial. Patients were eligible if they had non-metastatic high-risk prostate cancer. All patients received 2.5 years of hormonal therapy and 46.5 Gy in 25 fractions to the pelvic lymph nodes. Patients received a radiation boost to the prostate, either before or after whole pelvic irradiation. Concurrent (20 mg/m2) Docetaxel was given on the first day of radiotherapy and weekly thereafter for a total of eight treatments until predefined toxicity stopping rules. Results: Ninety patients were included and randomized. Four were ineligible for the analysis. In total, 42 patients were randomized to the standard sequence, 44 patients to the experimental sequence. There were statistically fewer GI or GU toxicities leading to a docetaxel dose reduction or omission in the experimental sequence compared to the standard sequence, 5 vs. 15 events (p = 0.027). There was no difference in overall survival, cause-specific survival, or biochemical-relapse free survival between the two sequences. Conclusions: This is the first study to test sequence inversion for pelvic radio-chemotherapy in a randomized double-blind trial. Less chemotherapy interruptions or dose reductions occurred by inverting the radiation sequence of the large field and the boost. The trial was registered with Clinicaltrials.gov: NCT00452556.

Surface Dosimetry of Patients Undergoing Total Body Irradiation: A Retrospective Analysis for Quality Assurance.

Total body irradiation (TBI) is used prior to bone marrow transplantation as part of the conditioning regimen in selected patients. A linear accelerator-based technique was used at our treatment centre between June, 2004 and August, 2015. Patients were treated supine with extended source-to-surface distance (SSD) lateral fields, and prescription dose was 12 Gy delivered in six fractions, two fractions per day. Dose was prescribed to midplane at the level of the umbilicus and monitor units were calculated manually based on measured beam data. Dose variation within 10% of the prescribed midplane dose is considered acceptable for TBI treatment. This was achieved in our clinic by using compensators to account for missing tissue in the head and neck and lower leg regions. Lung attenuators were routinely used to correct for internal inhomogeneity, which resulted from low density lung tissue. The purpose of this study was to determine whether dose variation was within acceptable limits for these patients as part of a quality assurance process. Following chart review, 129 patients who received six-fraction TBI from 2004 to 2015 were included in this study. Patients receiving single fraction treatment were excluded. Metal oxide semiconductor field effect transistors (MOSFET) dosimetry was used to measure surface dose at four or five locations during patients' first fraction of TBI. Dosimetry was repeated during the second fraction for any site with variation greater than 10%. Statistical analysis was carried out on patient data, diagnosis and dosimetry measurements. Of the 129 patients who met the inclusion criteria, 50 were diagnosed with acute myelogenous leukemia, 30 with acute lymphoblastic leukemia and 11 with chronic myelogenous leukemia. The rest of the patients were diagnosed with lymphoma or myelodysplastic syndromes. The mean percent variation in dosimetry measurements taken at the specific locations ranged between 3.5% and 8.3%. The highest variation was found in measurements performed on the cheek. A high percentage of all dosimetry readings (85.5%) was within the acceptable range of +10% from the expected value. The highest number of individual readings taken at a specific location that fell outside this range were found at the cheek. We conclude that the linear accelerator delivered TBI at our centre meets the acceptable limits of dose variation over an 11-year period.

Current Mental Distress Among Men With a History of Radical Prostatectomy and Related Adverse Correlates.

Recent reviews and observational studies have reported that patients with prostate cancer (PCa) are at increased risk of mental health issues, which in turn negatively affects oncological outcomes. Here, we examine possible explanatory variables of mental distress in a population-based cohort of men who have undergone radical prostatectomy (RP). Data were derived from a Maritimes-Canada online survey assessing patient-reported quality of life outcomes between 2017 and 2019 administered to 136 men (47-88 years old, currently in a relationship) who have undergone RP for their PCa diagnosis. The primary outcome was a validated assessment of mental distress, the Kessler Psychological Distress Scale (K10). Urinary function was assessed using the International Prostate Symptom Score, and relationship satisfaction was assessed using the Dyadic Assessment Scale. A multivariate logistic regression assessed the contribution of urinary function, relationship satisfaction, age, multimorbidity, additional treatments, medication for depression and/or anxiety, and survivorship time. A total of 16.2% men in this sample screened positive for mental distress. The severity of urinary problems was positively associated with increased mental distress (OR = 4.79, 95% CI [1.04, 22.03]), while increased age (OR = 0.87, 95% CI [0.78, 0.97]), relationship satisfaction (OR = 0.14, 95% CI [0.3, .077]), and current medication for anxiety, depression, or both (OR = 0.09, 95% CI [0.02, 0.62]) were protective factors. Survivorship time, the presence of additional comorbidities, or PCa treatments were not identified to be statistically significant contributions to the fitted model. Here, we report that RP survivors are prone to presenting with increased mental distress long after treatment. Screening for mental distress during RP survivorship is recommended.

An Examination of the Relationship between Mental Distress, Functional and Psychosocial Quality of Life Indicators in a Population Based Sample of Prostate Cancer Survivors Who Received Curative Treatment.

INTRODUCTION: Although survival rates are highest among prostate cancer survivors compared to any other forms of cancer, nearly 60% suffer from mental distress. Here we examine urinary function and psychosocial stressors and their association with poor mental health in a younger group of prostate cancer survivors who have undergone curative treatment. METHODS: The study includes 128 men (47 to 70 years old) who received active treatment for prostate cancer, and completed a survivorship online survey between 2017 and 2018. Psychological distress was assessed with Kessler Psychological Distress Scale. International Prostate Symptom Score subscales (incomplete urinary emptying, frequency, intermittency, urgency, weak stream, straining and nocturia) and number of current prostate cancer survivorship stressors were predictors. Multivariate logistic regression was used to fit the model while controlling for months of survivorship since diagnosis, the presence or absence of surgery, radiation or hormone therapy treatment, current medication for depression and demographics. RESULTS: A total of 19.5% of men scored positive for current mental health issues. Prostate cancer survivors who reported increased number of current survivorship stressors (OR 1.48, 95% CI 1.09-2.01), had higher frequency of urination (OR 2.05, 95% CI 1.15-3.64), history of radiation treatment (OR 7.15, 95% CI 1.02-50.35) and were currently on prescribed medication for depression (OR 33.47, 95% CI 3.80-294.87) had higher odds for screening positive for psychological distress compared with their counterparts. CONCLUSIONS: These results corroborate recent findings showing an intersection between urological oncology and poor mental health during survivorship, and warrant the development of multidisciplinary teams in addressing survivorship issues in this population.

Risk stratification models in human papillomavirus-associated oropharyngeal squamous cell carcinoma: the Nova Scotia distribution.

OBJECTIVE: The incidence of oropharyngeal squamous cell carcinoma is increasing with a growing proportion of diagnoses associated with human papillomavirus (p16 + OSCC), which generally confers a favorable prognosis. For these reasons, novel risk stratification models specific to the p16 + OSCC population have recently been proposed to guide future research on treatment de-intensification for appropriate patients. This study aimed to quantify patient risk distribution using multiple published risk models and investigate the hypothesis that the local p16 + OSCC population includes a smaller proportion of low-risk patients due to a high prevalence of concurrent tobacco exposure. METHODS: A retrospective cohort study was performed including patients diagnosed with p16 + OSCC in Nova Scotia between 2011 and 2015. Patient identification was obtained through the CCNS registry and an institutional database. Exclusion criteria included HPV negative status, second primary cases, incomplete data availability, and local recurrence cases. RESULTS: Following exclusion, 117 patients met study criteria. The majority had small primary tumors (70.9% ≤ T2) and advanced nodal status on presentation (60.7% ≥ N2b). Most patients had a positive smoking history (62.4%), with 53.0% of patients having a pack-year history greater than 10 pack-years. In four of the five risk stratification models, the majority of the study population fell into the lowest risk category. The risk stratification distribution of our local population was similar to the populations used to validate the published models, with the largest single category difference being 13.3% (range - 12.3 to + 13.3%). CONCLUSIONS: This is the first study to compare multiple currently published risk stratification models to a local population and address the uncertainty of risk stratification in the Nova Scotian p16 + OSCC population. Despite a high prevalence of concurrent tobacco exposure, the study population was found to be overall low risk, with similar risk compared to model validation populations.