Sujay A. Vora

INITIAL EXPERIENCE WITH ULTRASOUND LOCALIZATION FOR POSITIONING PROSTATE CANCER PATIENTS FOR EXTERNAL BEAM RADIOTHERAPY

PURPOSE Transabdominal ultrasound localization of the prostate gland and its immediate surrounding anatomy has been used to guide the positioning of patients for the treatment of prostate cancer. This process was evaluated in terms of (1) the reproducibility of the ultrasound measurement; (2) a comparison of patient position between ultrasound localization and skin marks determined from a CT treatment planning scan; (3) the predictive indicators of patient anatomy not well suited for ultrasound localization; (4) the measurement of prostate organ displacement resulting from ultrasound probe pressure; and (5) quality assurance measures. METHODS AND MATERIALS The reproducibility of the ultrasound positioning process was evaluated for same-day repeat positioning by the same ultrasound operator (22 patients) and for measurements made by 2 different operators (38 patients). Differences between conventional patient positioning (CT localization with skin markings) and ultrasound-based positioning were determined for 38 patients. The pelvic anatomy was evaluated for 34 patients with pretreatment CT scans to identify predictors of poor ultrasound image quality. The displacement of the prostate resulting from pressure of the ultrasound probe was measured for 16 patients with duplicate CT scans with and without a simulated probe. Finally, daily, monthly, and semiannual quality assurance tests were evaluated. RESULTS Self-verification tests of ultrasound positioning indicated a shift of <3 mm in approximately 95% of cases. Interoperator tests indicated shifts of <3 mm in approximately 80-90% of cases. The mean difference in patient positioning between conventional and ultrasound localization for lateral shifts was 0.3 mm (SD 2.5): vertical, 1.3 mm (SD 4.7 mm) and longitudinal, 1.0 mm (SD 5.1). However, on a single day, the differences were >10 mm in 1.5% of lateral shifts, 7% of longitudinal shifts, and 7% of vertical shifts. The depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis, but not the bladder volume, were significant predictive indicators of poor ultrasound imaging. The pressure of the ultrasound probe displaced the prostate in 7 of the 16 patients by an average distance of 3.1 mm; 9 patients (56%) showed no displacement. Finally, the quality assurance tests detected ultrasound equipment defects. CONCLUSION The ultrasound positioning system is reproducible and may indicate the need for significant positioning moves. Factors that predict poor image quality are the depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis. The prostate gland may be displaced a small amount by the pressure of the ultrasound probe. A quality assurance program is necessary to detect ultrasound equipment defects that could result in patient alignment errors.

Radiation dose escalation for localized prostate cancer: Intensity-modulated radiotherapy versus permanent transperineal brachytherapy

In the current study, the effects of dose escalation for localized prostate cancer treatment with intensity‐modulated radiotherapy (IMRT) or permanent transperineal brachytherapy (BRT) in comparison with conventional dose 3‐dimensional conformal radiotherapy (3D‐CRT) were evaluated.

Outcome and Toxicity for Patients Treated with Intensity Modulated Radiation Therapy for Localized Prostate Cancer

PURPOSE We evaluate long-term disease control and chronic toxicities observed in patients treated with intensity modulated radiation therapy for clinically localized prostate cancer. MATERIALS AND METHODS A total of 302 patients with localized prostate cancer treated with image guided intensity modulated radiation therapy between July 2000 and May 2005 were retrospectively analyzed. Risk groups (low, intermediate and high) were designated based on National Comprehensive Cancer Network guidelines. Biochemical control was based on the American Society for Therapeutic Radiology and Oncology (Phoenix) consensus definition. Chronic toxicity was measured at peak symptoms and at last visit. Toxicity was scored based on Common Terminology Criteria for Adverse Events v4. RESULTS The median radiation dose delivered was 75.6 Gy (range 70.2 to 77.4) and 35.4% of patients received androgen deprivation therapy. Patients were followed until death or from 6 to 138 months (median 91) for those alive at last evaluation. Local and distant recurrence rates were 5% and 8.6%, respectively. At 9 years biochemical control rates were 77.4% for low risk, 69.6% for intermediate risk and 53.3% for high risk cases (log rank p = 0.05). On multivariate analysis T stage and prostate specific antigen group were prognostic for biochemical control. At last followup only 0% and 0.7% of patients had persistent grade 3 or greater gastrointestinal and genitourinary toxicity, respectively. High risk group was associated with higher distant metastasis rate (p = 0.02) and death from prostate cancer (p = 0.0012). CONCLUSIONS This study represents one of the longest experiences with intensity modulated radiation therapy for prostate cancer. With a median followup of 91 months, intensity modulated radiation therapy resulted in durable biochemical control rates with low chronic toxicity.

Acute and chronic results of adjuvant radiotherapy after mastectomy and Transverse Rectus Abdominis Myocutaneous (TRAM) flap reconstruction for breast cancer.

A retrospective review of the treatment of 15 breast cancer patients who received postoperative radiotherapy after a mastectomy and transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction was undertaken to determine the effects of postoperative irradiation on flap viability and cosmesis. Fourteen patients had pedicle TRAM flaps, and one patient had a free TRAM flap. Surgical complications, acute and chronic side effects of radiotherapy, and cosmetic outcome were evaluated. The median interval between the TRAM flap procedure and radiotherapy was 7 months. The median total radiation dose was 60 Gy. All patients underwent three-dimensional radiotherapy treatment planning to determine the optimal dose distribution. Mild erythema developed in 9 patients (60%), moderate erythema developed in 2 (13%), and severe erythema developed in 1 (7%). Dry desquamation developed in 6 patients (40%), whereas moist desquamation developed in none. At median follow-up of 26.4 months, only 2 (13%) of the 15 patients had fat necrosis within the TRAM flap that was not present before radiotherapy. Fourteen patients (93%) retained their flap, and 13 patients (87%) rated their cosmetic outcome as “good” to “excellent.” We conclude that TRAM flaps can be irradiated with few complications and acceptable cosmetic results.

Prostate brachytherapy seed embolization to the right renal artery.

PURPOSE We report three cases of seed embolization to the right renal artery after iodine-125 (I-125) transperineal interstitial permanent prostate brachytherapy. METHODS AND MATERIALS Case 1: A 65-year-old man presented with right flank and back pain less than 4 months after prostatic seed implantation. CT evaluation for renal stone showed a seed embedded in the lower aspect of the right kidney. Case 2: A 73-year-old man complained of painless hematuria 3 years after prostatic seed brachytherapy. CT and subsequent abdominal angiography showed a seed embolization to a lower branch of the right renal artery. Case 3: An 84-year-old man presented with gross hematuria 7 months after prostatic seed implantation. Excretory urogram and subsequent CT demonstrated the right lower renal seed migration. RESULTS Prostatic seed embolization to the right renal artery may cause pain and hematuria. This pattern of seed migration may be easily overlooked by imagers because it mimics renal lithiasis on cross-sectional imaging. Knowledge of prior history of permanent interstitial prostate brachytherapy and careful radiologic interpretation may help to achieve the correct diagnosis of rare renal seed migration. CONCLUSIONS We present an additional atypical site of brachytherapy seed relocation in the right renal artery in 3 patients. This type of migration is probably secondary to pulmonary arteriovenous malformation or right-to-left cardiac shunts. Awareness of the propensity of seeds to dislodge and vigilance in imaging interpretation of prostatic brachytherapy recipients are necessary for the correct diagnosis of seed embolization.

Prophylactic cranial irradiation in elderly patients with small cell lung cancer: Findings from a North Central Cancer Treatment Group pooled analysis

OBJECTIVES To examine the efficacy of prophylactic cranial irradiation (PCI) in elderly patients with small cell lung cancer (SCLC) (≥70 years of age) from a pooled analysis of four prospective trials. MATERIALS & METHODS One hundred fifty-five patients with SCLC (limited stage, LSCLC, and extensive stage, ESCLC) participated in four phase II or III trials. Ninety-one patients received PCI (30 Gy/15 or 25 Gy/10) and 64 patients did not receive PCI. Survival was compared in a landmark analysis that included only patients who had stable disease or better in response to primary therapy. RESULTS Patients who received PCI had better survival than patients who did not receive PCI (median survival 12.0 months vs. 7.6 months, 3-year overall survival 13.2% vs. 3.1%, HR = 0.53 [95% CI 0.36-0.78], p = 0.001). On multivariate analysis of the entire cohort, the only factor that remained significant for survival was stage (ESCLC vs. LSCLC, p = 0.0072). In contrast, the multivariate analysis of patients who had ESCLC revealed that PCI was the sole factor associated with a survival advantage (HR = 0.47 [95% CI 0.24-0.93], p = 0.03). Grade 3 or higher adverse events (AEs) were significantly greater in patients who received PCI (71.4% vs. 47.5%, p = 0.0031), with non-neuro and non-heme being the specific AE categories most strongly correlated with PCI delivery. CONCLUSIONS PCI was associated with a significant improvement in survival for our entire elderly SCLC patient cohort on univariate analysis. Multivariate analysis suggested that the survival advantage remained significant in patients with ESCLC. PCI was also associated with a modest increase in grade 3 or higher AEs.

Image-Guided Radiotherapy for Prostate Cancer: A Prospective Trial of Concomitant Boost Using Indium-111–Capromab Pendetide (ProstaScint) Imaging

PURPOSE To evaluate, in a prospective study, the use of (111)In-capromab pendetide (ProstaScint) scan to guide the delivery of a concomitant boost to intraprostatic region showing increased uptake while treating the entire gland with intensity-modulated radiotherapy for localized prostate cancer. METHODS AND MATERIALS From September 2002 to November 2005, 71 patients were enrolled. Planning pelvic CT and (111)In-capromab pendetide scan images were coregistered. The entire prostate gland received 75.6 Gy/42 fractions, whereas areas of increased uptake in (111)In-capromab pendetide scan received 82 Gy. For patients with T3/T4 disease, or Gleason score ≥8, or prostate-specific antigen level >20 ng/mL, 12 months of adjuvant androgen deprivation therapy was given. In January 2005 the protocol was modified to give 6 months of androgen deprivation therapy to patients with a prostate-specific antigen level of 10-20 ng/mL or Gleason 7 disease. RESULTS Thirty-one patients had low-risk, 30 had intermediate-risk, and 10 had high-risk disease. With a median follow-up of 66 months, the 5-year biochemical control rates were 94% for the entire cohort and 97%, 93%, and 90% for low-, intermediate-, and high-risk groups, respectively. Maximum acute and late urinary toxicities were Grade 2 for 38 patients (54%) and 28 patients (39%) and Grade 3 for 1 and 3 patients (4%), respectively. One patient had Grade 4 hematuria. Maximum acute and late gastrointestinal toxicities were Grade 2 for 32 patients (45%) and 15 patients (21%), respectively. Most of the side effects improved with longer follow-up. CONCLUSION Concomitant boost to areas showing increased uptake in (111)In-capromab pendetide scan to 82 Gy using intensity-modulated radiotherapy while the entire prostate received 75.6 Gy was feasible and tolerable, with 94% biochemical control rate at 5 years.

Six-year Outcome of a Prospective Study Evaluating Tumor Bed Boost with Intra-operative Electron Irradiation Followed by whole-Breast Irradiation for Early-Stage Breast Cancer

A prospective study was performed for patients with early‐stage breast cancer in which a single fraction of intraoperative electron irradiation (IOERT) was given to the tumor bed, followed by conventional fractionated whole‐breast irradiation (WBRT). Patients with T1/T2N0 breast cancer underwent lumpectomy and sentinel lymph node biopsy. A tumor bed boost of 10 Gy of IOERT using 6–12 MeV electrons was administered by a dedicated mobile linear accelerator in the operating room. After adequate wound healing, 48 Gy WBRT was given to the whole breast in 24 fractions. Fifty‐two patients were enrolled between February 2003 and January 2005. At a median follow‐up of 79 months, there were two local relapses. The 6‐year actuarial overall survival and distant control rates were 89% and 96%, respectively. At last follow‐up, cosmesis was graded as excellent or good in 45 (87%), fair in five (10%), and poor in two patients (4%), respectively. Difficulty in wound healing occurred in two patients who had additional surgery later. One patient developed significant fibrosis after aspiration of a symptomatic seroma. The result of this pilot study shows the feasibility of using IOERT as the tumor bed boost in lieu of 6–8 days of standard electron beam treatment with good local control and cosmetic results. However, late surgical intervention of the lumpectomy bed may result in more pronounced tissue fibrosis and wound healing difficulty.

Factors Associated With Survival Following Radium-223 Treatment for Metastatic Castration-resistant Prostate Cancer

Micro‐Abstract The outcomes of 64 patients with metastatic castration‐resistant prostate cancer after treatment with radium‐223 were analyzed. Four factors were identified to be associated with survival in multivariate analysis. Future studies to evaluate earlier use of this radiopharmaceutical in newly diagnosed metastatic prostate cancer when the disease is sensitive to androgen deprivation therapy would be warranted. Background: Radium‐223 (223Ra) improves survival in patients with metastatic castration‐resistant prostate cancer (mCRPC). This retrospective analysis was performed to better understand its efficacy in routine clinical practice and identify factors associated with survival. Materials and Methods: Sixty‐four patients with mCRPC who received 223Ra between 2013 and 2015 were the basis of this retrospective study. Clinical outcomes and patient characteristics were obtained. Potential prognostic factors for survival were evaluated by univariate analysis using the log‐rank test and multivariate analysis using the Cox proportional hazard method. Results: The median survival was 12.9 months. Twenty‐one patients (33%) developed a skeletal event, and the median time to the first skeletal event was 4.4 months. In univariate analysis, factors significantly associated with survival included: no prior chemotherapy, ≤ 5 bone metastases, baseline prostate‐specific antigen (PSA) ≤ 36 ng/mL, baseline alkaline phosphatase (ALP) < 115 U/L, baseline hemoglobin > 12 g/dL, ALP response after 223Ra treatment, PSA decrease during 223Ra treatment, and absence of > 25% PSA increase during 223Ra treatment. In multivariate analysis, 4 factors remained significant: no prior chemotherapy, ≤ 5 bone metastases, baseline ALP < 115 U/L, and ALP response after 223Ra treatment. Conclusion: When 223Ra is administered in routine clinical practice, clinical outcomes can be more variable than those reported in the randomized study owing to patient heterogeneity. Four factors were identified to be significantly associated with survival after 223Ra treatment. These pretreatment factors may be used as stratification factors in future studies to investigate whether 223Ra would be more effective for patients with newly diagnosed metastatic disease that is sensitive to androgen deprivation therapy.

Patient Specific Characteristics Are an Important Factor That Determines the Risk of Acute Grade ≥ 2 Rectal Toxicity in Patients Treated for Prostate Cancer with IMRT and Daily Image Guidance Based on Implanted Gold Markers

Aim To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics. Methods A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models. Results Sixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1–0.16), slope m=0.09 (0.08–0.11), and threshold dose TD50=56.8 (53.7–59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was PSAtox = 5.77 ± 2.27 and it was PSAnotox = 9.5 ± 7.8 for the remainder (p=0.01). Conclusions Patient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer.