Mark L. Sobczak

Prostate Bed Motion during Intensity Modulated Radiotherapy Treatment

PURPOSE Conformal radiation therapy in the postprostatectomy setting requires accurate setup and localization of the prostatic fossa. In this series, we report prostate bed localization and motion characteristics, using data collected from implanted radiofrequency transponders. METHODS AND MATERIALS The Calypso four-dimensional localization system uses three implanted radiofrequency transponders for daily target localization and real-time tracking throughout a course of radiation therapy. We reviewed the localization and tracking reports for 20 patients who received ultrasonography-guided placement of Calypso transponders within the prostate bed prior to a course of intensity-modulated radiation therapy at Fox Chase Cancer Center. RESULTS At localization, prostate bed displacement relative to bony anatomy exceeded 5 mm in 9% of fractions in the anterior-posterior (A-P) direction and 21% of fractions in the superior-inferior (S-I) direction. The three-dimensional vector length from skin marks to Calypso alignment exceeded 1 cm in 24% of all 652 fractions with available setup data. During treatment, the target exceeded the 5-mm tracking limit for at least 30 sec in 11% of all fractions, generally in the A-P or S-I direction. In the A-P direction, target motion was twice as likely to move posteriorly, toward the rectum, than anteriorly. Fifteen percent of all treatments were interrupted for repositioning, and 70% of patients were repositioned at least once during their treatment course. CONCLUSION Set-up errors and motion of the prostatic fossa during radiotherapy are nontrivial, leading to potential undertreatment of target and excess normal tissue toxicity if not taken into account during treatment planning. Localization and real-time tracking of the prostate bed via implanted Calypso transponders can be used to improve the accuracy of plan delivery.

Impact of obesity on outcomes after definitive dose-escalated intensity-modulated radiotherapy for localized prostate cancer

Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose‐escalated RT.

Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer

We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, stereotactic body RT [SBRT]) and brachytherapy (BT), with an emphasis on the outcomes, toxicities, and contraindications for therapies. PICOS/PRISMA methods were used to identify published English-language comparative studies on PubMed (from 1980 to 2015) that included men treated on prospective studies with a primary endpoint of patient outcomes, with ⩾70 patients, and ⩾5year median follow up. Twenty-six studies met inclusion criteria; of these, 16 used EBRT, and 10 used BT. Long-term freedom from biochemical failure (FFBF) rates were roughly equivalent between conventional and hypofractionated RT with intensity modulation (evidence level 1B), with 10-year FFBF rates of 45-90%, 40-60%, and 20-50% (for low-, intermediate-, and high-risk groups, respectively). SBRT had promising rates of BF, with shorter follow-up (5-year FFBF of >90% for low-risk patients). Similarly, BT (5-year FFBF for low-, intermediate-, and high-risk patients have generally been >85%, 69-97%, 63-80%, respectively) and BT+EBRT were appropriate in select patients (evidence level 1B). Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82-97%, 1-14%, 0-8%, respectively) have not been detected in randomized trials of dose escalation or in studies comparing RT modalities. Studies did not use patient-reported outcomes, through Grade 3-4 toxicities were rare (<5%) among all modalities. There was limited evidence available to compare proton therapy to other modalities. The treatment decision for a man is usually based on his risk group, ability to tolerate the procedure, convenience for the patient, and the anticipated impact on quality of life. To further personalize therapy, future trials should report (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education status; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics.

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder‐preservation therapy for muscle‐invasive bladder cancer

The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder‐preservation therapy (BPT) for muscle‐invasive urothelial carcinoma of the bladder.

Prostate Cancer Patients With Unmanaged Diabetes or Receiving Insulin Experience Inferior Outcomes and Toxicities After Treatment With Radiation Therapy

Micro‐Abstract We evaluated the effect of type 2 diabetes, and medications used in its management, on prostate cancer patients receiving radiation therapy. Men who were receiving insulin and those not receiving any medication had increased risk of death and toxicity than those without diabetes. Background: The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy. Patients and Methods: We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer‐specific survival, and toxicities. Kaplan–Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used. Results: Of the 3217 patients, 1295 (40%) were low‐risk, 1192 (37%) were intermediate‐risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow‐up time was 50 (range, 1‐190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66‐1.54), BF (sHR, 2.14; 0.88‐1.83), and cause‐specific mortality (sHR, 3.87; 95% CI, 1.31‐11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%‐14% vs. 2%‐6%; P < .01). Conclusion: Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients. Graphical abstract: Figure. No Caption available.

A comparison of robotic arm versus gantry linear accelerator stereotactic body radiation therapy for prostate cancer

Prostate cancer is the most prevalent cancer diagnosed in men in the United States besides skin cancer. Stereotactic body radiation therapy (SBRT; 6–15 Gy per fraction, up to 45 minutes per fraction, delivered in five fractions or less, over the course of approximately 2 weeks) is emerging as a popular treatment option for prostate cancer. The American Society for Radiation Oncology now recognizes SBRT for select low- and intermediate-risk prostate cancer patients. SBRT grew from the notion that high doses of radiation typical of brachytherapy could be delivered noninvasively using modern external-beam radiation therapy planning and delivery methods. SBRT is most commonly delivered using either a traditional gantry-mounted linear accelerator or a robotic arm-mounted linear accelerator. In this systematic review article, we compare and contrast the current clinical evidence supporting a gantry vs robotic arm SBRT for prostate cancer. The data for SBRT show encouraging and comparable results in terms of freedom from biochemical failure (>90% for low and intermediate risk at 5–7 years) and acute and late toxicity (<6% grade 3–4 late toxicities). Other outcomes (eg, overall and cancer-specific mortality) cannot be compared, given the indolent course of low-risk prostate cancer. At this time, neither SBRT device is recommended over the other for all patients; however, gantry-based SBRT machines have the abilities of treating larger volumes with conventional fractionation, shorter treatment time per fraction (~15 minutes for gantry vs ~45 minutes for robotic arm), and the ability to achieve better plans among obese patients (since they are able to use energies >6 MV). Finally, SBRT (particularly on a gantry) may also be more cost-effective than conventionally fractionated external-beam radiation therapy. Randomized controlled trials of SBRT using both technologies are underway.

Young age under 60 years is not a contraindication to treatment with definitive dose escalated radiotherapy for prostate cancer

BACKGROUND It is widely believed that younger prostate cancer patients are at greater risk of recurrence following radiotherapy (RT). METHODS From 1992 to 2007, 2168 (395 age ≤ 60) men received conformal RT alone for prostate cancer at our institution (median dose=76 Gy, range: 72-80). Multivariable analysis (MVA) was used to identify significant predictors for BF and PCSM. Cumulative incidence was estimated using the competing risk method (Fine and Gray) for BF (Phoenix definition) and PCSM to account for the competing risk of death. RESULTS With a median follow-up of 72.2 months (range: 24.0-205.1), 8-year BF was 27.1% for age ≤ 60 vs. 23.7% for age >60 (p=0.29). Eight-year PCSM was 3.0% for age ≤ 60 vs. 2.0% for age >60 (p=0.52). MVA for BF identified initial PSA [adjusted HR=1.7 (PSA 10-20), 2.6 (PSA >20), p<0.01], Gleason score [adjusted HR=2.1 (G7), 1.9 (G8-10), p<0.01], T-stage [adjusted HR=1.7 (T2b-c), 2.6 (T3-4), p<0.01], and initial androgen deprivation therapy (ADT) [adjusted HR=0.38 (ADT >12 months), p<0.01] as significant, but not age or ADT <12 months. MVA for PCSM identified Gleason score [adjusted HR=3.0 (G8-10), p=0.01] and T-stage [adjusted HR=8.7 (T3-4), p<0.01] as significant, but not age, PSA, or ADT. CONCLUSION This is the largest, most mature study of younger men treated with RT for prostate cancer that confirms young age is not prognostic for BF.

Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT),...

Effects of interruptions of external beam radiation therapy on outcomes in patients with prostate cancer

To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa).

Effects of interruptions of radiotherapy on outcomes of patients with prostate cancer.

37 Background: To evaluate if interruptions of radiotherapy have any effect on outcomes for men with localized prostate cancer (PCa) treated with definitive external beam radiation therapy (EBRT). Methods: We included men with localized PCa treated with definitive 3DCRT or IMRT of escalated dose (≥74 Gy in daily fraction of 2 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) between 1989 and 2013. Men receiving androgen deprivation therapy, or follow up <1 year were excluded. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of therapy, to account for the difference in total RT dose and planned RT duration. NTDR was analyzed for each NCCN risk group. Results: A total of 1,796 men including 861 low risk, 821 intermediate risk, and 114 high risk were included, with median follow up of 53.5 m (range 12 to 185.8 m). The median NTDR was 31% (range 23.1%-71.2%), translating to approximately 2 breaks (each break represents a missed treatment that would b...