Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis.

AIMS: There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure. MATERIALS AND METHODS: Individual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases. RESULTS: Six hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9-7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5-31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1-311.6, P = 0.003). CONCLUSION: 4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

Survey of current practices from an international task force for gynecological stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.

Dose-volume factors to select patient-specific image-guidance action thresholds in prostate cancer.

For radiation delivery tracking systems that monitor intrafraction prostate motion, generalized departmental threshold protocols may be used. The purpose of this study is to determine whether predefined action thresholds can be generally applied or if patient-specific action thresholds may be required. Software algorithms were developed in the MatLab (The Mathworks Inc., Natick, MA) software environment to simulate shifts of the patient structure set consisting of prostate, bladder, and rectum. These structures were shifted by 1/2 10 mm in each direction in 1 mm increments to simulate displacements during treatment, without taking into consideration organ deformity. Dose-volume data at each shift were plotted and analyzed. A linear relationship was observed between planning dose-volume parameters and shifted dose-volume parameters. For a 5 mm anterior shift, it was observed that individual rectal V70 values increased by absolute magnitudes of 6-15%, dependent on the planning rectal V70 of each patient. Likewise, for a 5 mm inferior shift, individual bladder V70 values increased by 1-14%, dependent on planning bladder V70. This linear relationship was observed for all levels of shifts up to 10 mm. Since rectum and bladder dose-volume changes due to patient shifts are dependent on dose-volume parameters, this study suggests that patient-specific action thresholds may be necessary.

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer.

PURPOSE: To determine overall survival, progression-free survival, rate of voice preservation, and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation. BACKGROUND: Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. PATIENTS AND METHODS: Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies. Induction treatment consisted of three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL-IFN) followed by surgery for residual disease. Surgical intent was to spare the larynx when possible. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy (FHX). RESULTS: A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report. Clinical CR was observed in 59% of patients following induction therapy. The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients. At five years, overall survival is 47%, progression-free survival is 78%, and locoregional control is 78%. No distant failures were observed. Voice preservation with disease control was 75% at five years. Only two total laryngectomies were performed during the course of treatment and follow-up. Treatment-related toxicity accounted for two deaths. CONCLUSIONS: The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome.

Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced oropharyngeal cancer.

PURPOSE: Locoregionally advanced oropharyngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. Herein, we report overall survival, progression-free survival, and patterns of failure in locoregionally advanced oropharyngeal cancer treated with induction chemotherapy with or without conservative surgery followed by concomitant chemoradiation. MATERIALS AND METHODS: Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin, and interferon alpha-2b (PFL-IFN) were followed by conservative, organ-sparing surgery for residual disease. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-fluorouracil, hydroxyurea, and a total radiotherapy dose of roughly 7,000 cGy. RESULTS: Sixty-one patients with predominantly stage IV disease were treated. Clinical complete response was observed in 65% of patients after induction therapy. The median follow-up was 68.0 months for survivors and 39.0 months for all patients. At 5 years, overall survival is 51%, progression-free survival is 64%, locoregional control is 70%, and distant control is 89%. Locoregional recurrence accounted for 80% of all initial failures. Only five radical surgeries (none were total glossectomy) were performed for initial disease control. Treatment-related toxicity accounted for four deaths. CONCLUSION: PFL-IFN given with 5-fluorouracil, hydroxyurea, and radiotherapy produces a high rate of cures with organ preservation in a disease group that has traditionally fared poorly. Local and distant disease control and survival rates exceed those observed with more standard treatment approaches involving surgery and radiotherapy. Further investigation into chemoradiotherapy as a curative modality for this disease is warranted.

Potency preservation following conformal radiotherapy for localized prostate cancer: impact of neoadjuvant androgen blockade, treatment technique, and patient-related factors.

PURPOSE: Impotence is a familiar sequela of both definitive external-beam radiotherapy (EBRT) and radical prostatectomy for localized prostate cancer. Among surgical options, nerve-sparing radical prostatectomy (NSRP) offers the highest potency preservation rate of 70%. We report the change in potency over time in an EBRT-treated population, determine the significantly predisposing health and treatment factors affecting post-EBRT potency, and compare age- and stage-matched potency rates with those of NSRP-treated patients. PATIENTS AND METHODS: Our results are from a retrospective study of 287 patients diagnosed with prostate cancer in clinical stages A to C and treated with conformal techniques to 6200 to 7380 cGy. Information regarding preradiotherapy potency, medical and surgical history, neoadjuvant antiandrogen use, and post-EBRT potency was documented for each patient. The median follow-up time was 34 months. RESULTS: At months 1, 20, 40, and 60, actuarial potency rates were 96%, 75%, 59%, and 53%, respectively. Factors identified as significant predictors of post-EBRT impotence include pre-EBRT partial potency, diabetes, coronary artery disease, and anti-androgen medication usage. Among treatment factors, a trend toward potency preservation was noted for the six-field versus the four-field technique. Finally, age- and stage-matched comparisons of potency rates for our population and NSRP-treated patients were performed. For patients older than 70 years, 60.9% of EBRT patients and 32.9% of NSRP patients remained potent after treatment. Overall, EBRT patient potency preservation was 71.3%, versus 66.2% for NSRP patients. DISCUSSION: Pre-EBRT partial potency, diabetes, coronary artery disease, and anti-androgen medication usage are significant predispositions to impotence in EBRT-treated prostate cancer patients. In comparing EBRT with NSRP for various age and stage groups, EBRT offers notably higher potency preservation rates than NSRP for patients older than 70 years.

Potency probability following conformal megavoltage radiotherapy using conventional doses for localized prostate cancer.

PURPOSE: Impotence is a familiar sequela of definitive external beam radiation therapy (EBRT) for localized prostate cancer; however, nerve-sparing radical prostatectomy (NSRP) has offered potency rates as high as 70% for selected for patients in several large series. To the authors' knowledge, age and stage-matched comparisons between the effects of EBRT and NSRP upon the normal age trend of impotence have not been performed. Herein, we report the change in potency over time in an EBRT-treated population, determine the significantly predisposing health factors affecting potency in this population, and compare age and stage-matched potency rates with those of normal males and prostatectomy patients. METHODS AND MATERIALS: Our results are obtained from a retrospective study of 114 patients ranging in age from 52 to 85 (mean, 68) who were diagnosed with clinical stages A-C C (T1-T4N0M0) prostate cancer and then treated conformally with megavoltage x-rays to 6500-7000 cGy (180-200 cGy per fraction) using the four-field box technique. Information concerning pre-RT potency, medical and surgical history, and medications was documented for each patient as was time of post-RT change in potency during regular follow-up. The median follow-up time was 18.5 months. RESULTS: The actuarial probability of potency for all patients gradually decreased throughout post-RT follow-up. At months 1, 12, 24, and 36, potency rates were 98, 92, 75, and 66%, respectively. For those patients who became impotent, the median time to impotence was 14 months. Factors identified from logistic regression analysis as significant predictors of post-EBRT impotence include pre-EBRT partial potency (p < 0.001), vascular disease (p < 0.001), and diabetes (p = 0.003). Next, an actuarial plot of potency probability to patient age for the EBRT-treated population was compared to that obtained from the Massachusetts Male Aging Study of normal males. The two curves were not significantly different (logrank test, p = 0.741) between ages 50 and 65. Finally, potency probability after follow-up of 1 year or more in EBRT-treated patients was stratified by age and substratified by clinical stage and then compared to similarly stratified potencies for patients treated with NSRP. The prostatectomy data were derived from the pooled data of six large (total n, 952), independent series conducted at academic centers. For patients older than 70 years, 79.1% of EBRT patients and 32.9% of NSRP patients remained potent after treatment. For patients with stage B2 disease, 75.0% of EBRT patients and 49.3% of NSRP patients remained potent after treatment. Overall EBRT patient potency was 76.1% vs. 66.2% for NSRP patients. CONCLUSIONS: 1) By 36 months after completion of EBRT for localized prostate cancer, fully one-third of all patients becomes impotent; however, for patients younger than 70 years, the probability of impotence does not depart significantly from that for normal males. 2) In the EBRT-treated population, pre-EBRT partial potency, vascular disease, and diabetes are the most significant predispositions to the development of impotence. Patients with these predispositions, though, do not become impotent significantly earlier than other patients. 3) When comparing age and stage-stratified potency rates for EBRT and NSRP patients, potency is roughly equal for both modalities for most age and stage groups; however, for patients older than 70 years or with stage B2 disease, EBRT offers notably higher posttreatment potency rates than NSRP. Thus, for the treatment of localized prostate cancer, EBRT may not affect the normal age trend of impotence in younger patients and may induce impotence less frequently than NSRP in older patients or in patients with later stage disease.