Jyoti Mayadev

Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group

Whats known on the subject? and What does the study add?

Role of Postmastectomy Radiation After Neoadjuvant Chemotherapy in Stage II-III Breast Cancer

PURPOSE To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). METHODS AND MATERIALS Seven breast cancer physicians from the University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. RESULTS Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤ 10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. CONCLUSIONS In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within the University of California Athena Breast Health Network.

A failure modes and effects analysis study for gynecologic high-dose-rate brachytherapy

PURPOSE To improve the quality of our gynecologic brachytherapy practice and reduce reportable events, we performed a process analysis after the failure modes and effects analysis (FMEA). METHODS AND MATERIALS The FMEA included a multidisciplinary team specifically targeting the tandem and ring brachytherapy procedure. The treatment process was divided into six subprocesses and failure modes (FMs). A scoring guideline was developed based on published FMEA studies and assigned through team consensus. FMs were ranked according to overall and severity scores. FM ranking >5% of the highest risk priority number (RPN) score was selected for in-depth analysis. The efficiency of each existing quality assurance to detect each FM was analyzed. RESULTS We identified 170 FMs, and 99 were scored. RPN scores ranged from 1 to 192. Of the 13 highest-ranking FMs with RPN scores >80, half had severity scores of 8 or 9, with no mode having severity of 10. Of these FM, the originating process steps were simulation (5), treatment planning (5), treatment delivery (2), and insertion (1). Our high-ranking FM focused on communication and the potential for applicator movement. Evaluation of the efficiency and the comprehensiveness of our quality assurance program showed coverage of all but three of the top 49 FMs ranked by RPN. CONCLUSIONS This is the first reported FMEA process for a comprehensive gynecologic brachytherapy procedure overview. We were able to identify FMs that could potentially and severely impact the patients treatment. We continue to adjust our quality assurance program based on the results of our FMEA analysis.

Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh as an alternative to tissue equivalent bolus

PURPOSE The use of brass mesh as a bolus is relatively uncommon in postmastectomy chest wall radiation therapy (PMRT). This study aimed to characterize the skin dose effects of using 2-mm fine brass mesh as an alternative to the traditional tissue-equivalent bolus during chest wall PMRT. METHODS AND MATERIALS Data were collected from patients who received PMRT using brass mesh at the University of California Davis Department of Radiation Oncology between January 2008 and June 2011. Several patient characteristics including age, body habitus, and ethnicity were analyzed along with several disease and treatment characteristics to determine whether or not they had an impact on the skin reaction observed during radiation treatment. Additionally, in vivo surface dose measurements were obtained for 16 of the 48 patients (33%). RESULTS Forty-eight female patients aged 28-83 received PMRT using brass mesh. As expected, the severity of skin toxicity increased with subsequent doses of radiation with all patients beginning treatment with no skin reaction (National Cancer Institute scores [NCIS] = 0) and the majority of patients completing treatment with either faint to moderate erythema (n = 19, 40%, NCIS = 1) or moderate to brisk erythema (n = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses between 81% and 122% of the prescribed dose, with an average of 99% of the prescribed radiation dose and standard deviation of 10% being delivered. CONCLUSIONS For postmastectomy chest wall radiation therapy, brass mesh is an effective alternative to tissue-equivalent bolus. The brass mesh achieved moderate erythema in the majority of patients at the end of treatment and the surface dose was validated using in vivo dosimetry.

Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

PURPOSE Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. METHODS AND MATERIALS Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. RESULTS Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. CONCLUSIONS A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

Interfraction motion of the vaginal apex during postoperative intensity modulated radiation therapy: are we missing the target?

Objective This study aimed to evaluate changes in vaginal cuff position and rectal distention during whole pelvic intensity modulated radiation therapy using daily image guidance for patients with gynecologic malignancies. Materials and Methods We reviewed 145 daily images from 5 patients treated with intensity modulated radiation therapy after total abdominal hysterectomy for endometrial or cervical cancer. A fiducial marker was placed in the vaginal cuff tissue before computed tomographic simulation. The 2008 ASTRO consensus guidelines for delineation of clinical target volumes were used to deliver 45 to 50 Gy to the target structures. Daily megavoltage computed tomographic images were reviewed and changes in position of the fiducial marker as compared to the initial planning scan were recorded in the anterior-posterior (AP), lateral, and superior-inferior dimensions. Changes in rectal distention were also recorded. The position of the fiducial marker relative to the planning target volumes was reviewed on each daily image. Results The average shifts of the gold seed in the AP, lateral, and superior-inferior dimensions were 7 mm (range, 0–28 mm), 3 mm (range, 0–7 mm), and 2.9 mm (range, 0–12 mm), respectively. Distention of the rectum ranged from 20.5 to 60.1 mm and correlated with movement of the gold seed in the AP dimension (R = 0.53). For 2 patients, the fiducial marker was within 5 mm of the planning target volume margin on 8/40 treatments, or outside the planning target volume on 4/40 treatments. This did not significantly impact total delivered dose to the planning target volume. Conclusions Daily image guidance confirms significant interfraction movement of the vaginal cuff tissue, which may exceed suggested guidelines for clinical target volume margins.

Permanent Prostate Brachytherapy in Prostate Glands <20 cm{sup 3}

PURPOSE To investigate the dosimetry, treatment-related morbidity, and biochemical outcomes for brachytherapy in patients with prostate glands <20 cm(3). METHODS AND MATERIALS From November 1996 to October 2006, 104 patients with prostate glands <20 cm(3) underwent brachytherapy. Multiple prostate, urethral, and rectal dosimetric parameters were evaluated. Treatment-related urinary and rectal morbidity were assessed from patient questionnaires. Cause-specific survival, biochemical progression-free survival, and overall survival were recorded. RESULTS The median patient age, follow up, and pre-treatment ultrasound volume was 64 years, 5.0 years and 17.6cm(3), respectively. Median day 0 dosimetry was significant for the following: V100 98.5%, D90 126.1% and R100 <0.5% of prescription dose. The mean urethral and maximum urethral doses were 119.6% and 133.8% of prescription. The median time to International Prostate Symptom Score resolution was 4 months. There were no RTOG grade III or IV rectal complications. The cause-specific survival, biochemical progression-free survival, and overall survival rates were 100%, 92.5%, and 77.8% at 9 years. For biochemically disease-free patients, the median most recent postbrachytherapy PSA value was 0.02 ng/mL. CONCLUSION Our results demonstrate that brachytherapy for small prostate glands is highly effective, with an acceptable morbidity profile, excellent postimplant dosimetry, acceptable treatment-related morbidity, and favorable biochemical outcomes.

Tolerance of the Small Bowel to Therapeutic Irradiation: A Focus on Late Toxicity in Patients Receiving Para-aortic Nodal Irradiation for Gynecologic Malignancies

Objective The recently published Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) recommends dose constraints for acute small-bowel toxicity but does not fully address dose constraints for late small-bowel toxicity and the maximum dose tolerance of the small bowel. Radiation oncologists in practice frequently face a challenge when deciding what maximum point dose to accept in a patient’s treatment plan. Given this lack of guidance for maximum radiation dose tolerance on the small bowel, we performed a literature search on the topic. Methods We searched PubMed for English language publications up to December 2012 on pelvic and para-aortic lymph node (PALN) irradiation for gynecologic malignancies. The search was performed using the following key words: late small-bowel toxicity, cervical cancer, endometrial cancer, ovarian cancer, gynecologic malignancies, pelvic irradiation, PALN irradiation, extended-field radiation therapy. Relevant references were selected, and full articles were obtained for review. The predetermined criteria for deciding which studies to include were used. Results With photon irradiation, the incidence of grade 3 or greater late small-bowel toxicity, including small-bowel obstruction, is 9% ± 7% after a median follow-up of 5 years and with mean pelvic and para-aortic/whole abdominal prescription doses of 50 ± 5 Gy and 40 ± 10 Gy, respectively. Our estimate for the small-bowel T10/5 would be the maximum point dose of 55 Gy. Conclusions If possible, it is prudent to try to keep the maximum point dose to the small bowel at 55 Gy or less. Given the lack of substantial data to make firm guidelines, further studies are needed to clarify the dose-volume relationship for late toxicity. Dose escalation to PALN should continue to be used with caution.

The impact of a vaginal brachytherapy boost to pelvic radiation in stage III endometrial cancer

Purpose We investigate the use and impact of a vaginal brachytherapy boost (VBB) after pelvic radiotherapy for stage III endometrial adenocarcinoma on vaginal and pelvic control. Material and methods One hundred patients treated from 1998-2011 with surgery and adjuvant therapy with or without a VBB were included. Variables examined were grade, stage, lymphovascular space invasion (LVSI), vaginal involvement (VI), cervical stromal involvement (CSI), myometrial invasion (MI), and a VBB. Failure was scored as vaginal, or pelvic. Fishers exact test assessed association between variables with vaginal and pelvic control. Results With a median follow up of 43 months, 31% were stage IIIA, 6% stage IIIB, and 63% stage IIIC. Thirty-eight (38%) received pelvic radiotherapy alone, and 62% received adjuvant chemotherapy. Of the 100 patients, 82 were treated with a VBB, 10 were not treated with a VBB, and 8 were not treated with RT. Of the 82 patients who received a VBB, 5 failed in the vagina with vaginal and pelvic control rates of 94% and 92%. The impact of VB reached borderline significance with its impact on pelvic control, 92% vs. 70% (p = 0.056), and did not affect vaginal control, 94% and 90% (p = 0.50). Neither tumor grade, LVSI, CSI, stage, nor LVSI (p > 0.05) statistically significantly impacted vaginal control. Conclusions There are no clinical guidelines for the use of a VBB in stage III endometrial cancer. The majority of our patients were treated with a VBB and experienced excellent pelvic and vaginal control. The presence of traditional adverse features did not negatively impact control in our patient cohort. However, the role of a VBB needs further investigation to understand the incremental benefit beyond pelvic RT.

Radiation treatment for patients with intermediate-risk prostate cancer.

Around 70% of men presenting with prostate cancer will have organ-confined disease, with the majority presenting with low- or intermediate-risk prostate cancer. This article reviews the evidence supporting the current standard of care in radiation oncology for the evaluation and management of men with intermediate-risk prostate cancer. Dose escalation, hormonal therapy, combined modality therapy, and modern techniques for the delivery of radiation therapy are reviewed.