Median V100 Research Articles

Endoscopy-guided brachytherapy for sinonasal and nasopharyngeal recurrences.

To evaluate the preliminary results of perioperative endoscopy-guided brachytherapy (BT) in recurrent sinonasal and nasopharyngeal tumors already treated for their primary tumor with a full course of radiotherapy. Patients with recurrence and already treated with a previous full course of radiotherapy >65Gy who underwent BT from December 2010 to January 2014 were taken into account for this work. Macroscopic disease was resected by an endoscopic approach, and catheters for BT were endoscopically positioned and fixed at the same time on the surgical bed. Surgery was performed under electromagnetic navigation guidance. The irradiation dose was 30Gy in 12 fractions, 2.5Gy each, twice a day, in 6days. We performed the endoscopy-guided BT 11 times in 9 patients; in two cases, no previous radiation therapy had been performed; and in one case, followup was too short to be considered. A total of 6 patients were eligible for the analysis. One patient underwent BT three times because of previous target margin recurrences. There were no immediate complications. The median and mean followups were 21 and 19months, respectively. The median V90 and V85% were 93% and 95%, respectively. In one case, we had a transient deficit of the VI cranial nerve (G3), and in another case, we diagnosed a noncomplicated osteonecrosis (G2). The median disease-free survival is 12months, and the median overall survival is 23months. The combination of endoscopy and BT seems to be a safe option for treating recurrent sinonasal and nasopharyngeal tumors.

Is it necessary to perform week three dosimetric analysis in low-dose-rate brachytherapy for prostate cancer when day 0 dosimetry is done? A quality assurance assessment.

To determine whether computed tomography/magnetic resonance imaging-based day 0 (d0) dosimetry is a meaningful predictor of day 21 (d21) dosimetry in low-dose-rate brachytherapy for localized prostate cancer. The study population consisted of 277 men with localized (T1-2 N0 M0), low-/intermediate-risk prostate cancer treated with low-dose-rate brachytherapy. Computed tomography/magnetic resonance imaging fusion was used for postimplant dosimetry at d0 and d21. Logistic regression was used to construct receiver operating characteristic curves for achieving each constraint at d21, based on d0 D90 and V100, and Youden's index was used to evaluate cutpoints. Freedom from biochemical failure (FBCF) was estimated with the Kaplan-Meier method. The median d0 D90 increased from 133 to 150Gy at d21, and median d0 V100 increased from 87% to 91%. For achieving the D90 constraint at d21, the optimal cut-point for d0 D90 was 135Gy, with 84% of these patients maintaining a d21 D90>145Gy. For achieving the D90 constraint at d21, the optimal cut-point for d0 V100 was 87%, with 83% of these patients maintained a d21 V100>90%. There was no improvement in FBCF in patients with a d0 D90>135Gy or D90>145Gy. Similarly, there was no improvement in FBCF in patients with a d0 V100>87% or V100>90%. Meeting dosimetric constraints on d0 does not obviate d21 dosimetric analysis. Constraints used for dose prescriptions on d0 are not the ideal predictors of d21 dosimetry.

Phase 1 Study of CT-Guided Interstitial 3-Dimensional (3D) Brachytherapy for Peripheral Non-Small Cell Lung Cancer

Phase 1 Study of CT-Guided Interstitial 3-Dimensional (3D) Brachytherapy for Peripheral Non-Small Cell Lung Cancer

Genetic Polymorphisms Associated With Toxicity Are Associated With Overall Survival Following Curative Radiation for Non-Small Cell Lung Cancer

To determine whether genetic polymorphisms previously associated with radiation esophagitis or pneumonitis following curative intent radiation therapy for NSCLC are associated with differences in overall survival. Between 2005-12, 280 patients with NSCLC treated with radiation or chemoradiation had blood samples stored for future analysis. Evaluating a candidate list of 19 genes (52 single nucleotide polymorphisms (SNPs), Illumina Golden Gate), our group identified associations between TNF-α (for CTCv3-G3+ esophagitis) and IL1-α (for CTCv3-G2+ radiation pneumonitis) using a training/validation approach accounting for clinical and dosimetric parameters in logistic models. The individual SNPs identified that showed a correlation with toxicity were tested for associations with overall survival using a Cox proportional hazard regression model (time-to-event) both individually and in conjunction. Major/minor allelic count was tested for increasing hazard via Kaplan-Meier estimates of each sub-group. For the 280 patients, 62% of patients were males with median age of 65 years; radiation treatment was 60-70 Gy; dosimetric analysis revealed median mean lung doses of 16.3 Gy, median V20 of 28.2 Gy, and median max esophageal dose of 66.7 Gy. During and after treatment 20% developed G2+ pneumonitis and 7% developed G3+ esophagitis. The three previously identified SNPs for esophagitis, were not associated with overall survival. The IL1-α SNP previously associated with pneumonitis risk was significantly associated with overall survival (HR: 0.58, 95%CI 0.35-0.96, p = 0.03). Patients with minor allelic variations were more likely to develop pneumonitis, but also were more likely to be alive during follow-up. When segregated by minor allele copy number (0 vs 1 vs 2), pneumonitis occurred more frequently (15% vs 22% vs 48%) and overall survival at three years was higher (72% vs 82% vs 90%). Genetic variations within the IL1-α cytokine response pathway were associated with both increased rates of G2+ radiation pneumonitis and higher rates of overall survival following curative radiation therapy for non-small cell lung cancer.

A PHASE II TRIAL OF BALLOON-CATHETER PARTIAL BREAST BRACHYTHERAPY OPTIMIZATION IN THE TREATMENT OF STAGE 0, I AND IIA BREAST CARCINOMA.

(a) To prospectively determine if multidwell position dose delivery can decrease skin dose and resultant toxicity over single dwell balloon-catheter partial breast irradiation, and (b) to evaluate whether specific skin parameters could be safely used instead of skin-balloon distance alone for predicting toxicity and treatment eligibility. A single-arm phase II study using a Simon two-stage design was performed on 28 women with stage 0-II breast cancer. All patients were treated with multiple dwell position balloon-catheter brachytherapy. The primary endpoint was ≥ grade 2 skin toxicity. Initial entry required a balloon-skin distance ≥ 7 mm. Based on the toxicity in the first 16 patients, additional patients were treated irrespective of skin-balloon distance as long as the Dmax to 1 mm skin thickness was < 130%. Compared to the phantom single dwell plans, multidwell planning yielded superior PTV coverage as per median V90, V95 and V100, but had slightly worse V150, V200 and DHI. Dmax to skin was decreased by multidwell planning at multiple skin thicknesses. The most common acute toxicity was grade 1 erythema (57%), and only two patients (7%) developed acute grade 2 toxicity (erythema). Late grade 1 fibrosis was seen in 32%. No patients experienced grade 3, 4, or 5 toxicity. Multidwell position planning for balloon-catheter brachytherapy results in lower skin doses with equal to superior PTV coverage and an overall low rate of initial skin toxicity. Our data suggest that limiting the Dmax to < 130% to 1 mm thick skin is achievable and results in minimal toxicity.

Minimally Invasive Intraoperative Multicatheter Breast Implant for Perioperative High-Dose-Rate Brachytherapy in Early Breast Cancer Treated With Conservative Surgery

To assess the safety and feasibility of MIOMBI in breast conservative surgery of breast cancer. Multicatheter Interstitial Breast Brachytherapy (MIBB) is an effective and safe technique for Accelerated Partial Breast Irradiation (APBI) in properly selected breast cancer patients treated with conservative surgery. MIBB technique allows reach the highest dose conformity and sparing healthy tissue ability respect of different APBI methods (Balloon, 3DCRT and Intraoperative Radiotherapy). MIBB is usually performed as closed-cavity procedure. This condition allows proper selection patients for APBI according to definitive pathological features but has some disadvantages since implies a second operation room visit for patient, determine a indirect visualisation of tumor bed with the consequently risk to make a geographical error dimmed frequently by performing extensive implants. Minimally Invasive Intraoperative Multicatheter Breast Implant (MIOMBI) represents an alternative to classic MIBB procedure with potential logistics, clinical and cosmetics advantages. Patients with early breast cancer candidates for conservative surgery were eligible for MIOMBI technique with 6F flexible catheters. Perioperative high-dose-rate brachytherapy (PHDRBT) was delivered as APBI (3.4 Gy for 10 in five days) in patients who met low- and intermediate-risk criteria according to GEC ESTRO recommendations, (women older than 40 years, infiltrating ductal carcinoma less than 2 cm with extensive intraductal carcinoma less than 25%, pN0, free margins more than 2mm and intraductal carcinoma less than 3 cm.) Those patients who did not meet previous criteria receive PHDRBT as anticipatory boost (4 fractions of 3.4 Gy in two days BAT) followed by hypofractionated whole breast irradiation 39.9 Gy in 15 fractions. From April 2010 to July 2013 101 consecutive breast cancer patients have been treated with conservative surgery and MIOMBI. The median time for MIOMBI procedure was 25 minutes. The median of number of catheter employed was 9 (4-14). No intraoperative complications were observed. Major complications RTOG grade 3-4 (acute and late) was observed only in one patient (1%) who suffered bleeding complication after implant remove. Infection (mastitis or abscess) was observed in 3 patients (2%). Fat necrosis with no symptoms was observed in 2 patients. PHDRBT was delivered as APBI in 64 patients (60%) and as a boost in 34 (40%). The median of CTV-T (clips zone plus 2 cm) was 41 cc with a median D90 of 3.27 Gy (96%) and DHI in CTV-T of 0.71. The median V100 and V150 was 60cc and 13cc, respectively, with a median DHI of 0.76. Median D10 in high-risk skin zone was 1.91 Gy (56%). With a median followup of 22 months (2-34) no (local, elsewhere, regional or distant) failure was observed. Cosmetic outcomes were evaluated in 46 of 64 APBI treatments (71%) with excellent and good results in 61% and 37%, respectively, and fair in 2%. Minimally invasive intraoperative multicatheter breast implant (MIOMBI) for perioperative high-dose-rate brachytherapy (PHDRBT) avoids a second surgical procedure, allows direct visualisation of tumor bed reducing the implant extension and keeps all advantages (dosimetric and proper selection patients for APBI) of the classic MIBB technique.

Multi-parametric MRI-guided focal tumor boost using HDR prostate brachytherapy: A feasibility study

This study investigates the feasibility of delivering focal boost dose to tumor regions, identified with multi-parametric MRI, in high-dose-rate prostate brachytherapy. T2-weighted, diffusion-weighted, and dynamic-contrast-enhanced MRI were acquired the day before treatment and analyzed retrospectively for 15 patients. Twelve patients had hormone therapy before the MRI scan. The tumor was delineated on MRI by a radiologist and registered to treatment planning transrectal ultrasound images. A margin based on analysis of delineation and registration uncertainties was applied to create a focal boost planning target volume (F-PTV). Delivered treatment plans were compared with focal boost plans optimized to increase F-PTV dose as much as allowed by urethral and rectal dose constraints. Tumors were delineated in all patients with volumes 0.4-23.0cc. The margin for tumor delineation and image registration uncertainties was estimated to be 4.5mm. For F-PTV, the focal boost treatment plans increased median D90 from 17.6 to 20.9Gy and median V150 from 27.3% to 75.9%. MRI-guided high-dose-rate prostate brachytherapy focal tumor boost is feasible-tumor regions can be identified even after hormone therapy, and focal boost dose can be delivered without violating urethral and rectal dose constraints.

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904

IntroductionStandard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. MethodsPatients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. Results100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p=0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p=0.05).). Furthermore, exposure of larger volumes of lung to lower (median V5=70%, p=0.09, median V10=63%, p=0.07), intermediate (median V20=50, p=0.04) and high (median V60=25%, p=0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose (median 31Gy) p=0.019. ConclusionPost-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Using Skin Dose Parameters Predicts Low Skin Toxicity in a Phase 2 Trial of Multiple Dwell Position Balloon-Based Brachytherapy for Partial Breast Irradiation

Purpose/Objective(s): Preliminary trials with balloon-based brachytherapy for partial breast irradiation showed a 50% rate of grade 2 or higher skin toxicity, and a substantial number of catheters had to be removed prior to treatment because of a balloon-skin distance <5 mm. These trials employed a “single dwell position” HDR technique. The objectives of this trial were: (a) to prospectively determine if a multiple dwell position dose delivery method can decrease skin dose and subsequent toxicity over an in silico modeled single dwell position technique while achieving similar or superior PTV coverage, and (b) to evaluate whether specific skin parameters could be safely used in lieu of skin-balloon distance alone for predicting toxicity and treatment eligibility. Materials/Methods: A single-arm phase II study using a Simon two-stage design was performed on 28 women with stage 0, I, or II (<3 cm) breast cancer. Each patient was treated using a multiple dwell position Ir-192 plan with a balloon-based applicator with a prescription of 3400 cGy in 10 fractions delivered BID. Initial entry required a minimum skin-balloon distance 7 mm. Plans for single dwell position treatment were also run for comparison of dosimetric parameters. The primary endpoint was grade 2 or higher skin toxicity. Acute and late toxicity was assessed during treatment and at 1, 3, 6, and 12 months. Based on the minimal toxicity seen after treating the first 16 patients, additional patients were treated irrespective of skin-balloon distance as long as the maximum dose to 1 mm thick skin tissue was <130%. Results: Compared to the phantom single dwell plans, multiple dwell position planning yielded equivalent to slightly superior PTV coverage as measured by median V90 (100% vs 97%, p < 0.001), V95 (99% vs 93%, p < 0.001), and V100 (96% vs 88%, p < 0.001) but had slightly higher median V150 (39% vs 29%, p < 0.001) and V200 (10% vs 4%, p < 0.001), as well as a lower median dose homogeneity index (0.6 vs 0.7, p Z 0.0046). Maximum point dose to skin was decreased by multiple dwell planning for all skin depths (1 mm, 2 mm, and 3 mm; p < 0.001). The most common grade 1 toxicities were erythema (16 pts), fibrosis (9 pts), fatigue (8 pts), mild pain (8 pts), hyperpigmentation (5 pts), and telangiectasias (4 pts). There have been 2 patients (7%) who developed grade 2 toxicity (both transient erythema), and no patients have experienced grade 3, 4, or 5 toxicity. Conclusions: Multiple dwell position planning for balloon-based brachytherapy results in lower skin doses with equal to superior PTV coverage and an overall low rate of skin toxicity. Our data suggest that limiting the maximum point dose to <130% to 1 mm thick skin is achievable and results in minimal toxicity independent of skin-balloon distance. This parameter may therefore be a more clinically relevant selection criterion. Author Disclosure: S.K. Nath: None. Z. Chen: None. B.P. Rowe: None. R. Blitzblau: None. S. Aneja: None. B.J. Grube: None. N. Horowitz: None. J.B. Weidhaas: None.

Implantation of Row One Needles 1-2 mm Anterior to the Posterior Margin of the Prostate Gland Results in Excellent PSA Control and Minimal Rectal Toxicity After I-125 Brachytherapy

Positioning of the posterior-most row of seeds (row 1) during prostate brachytherapy (PB) determines dose coverage to both the cancer-prone posterior peripheral zone and the anterior rectal wall and therefore impacts cure rates as well as the incidence of late rectal toxicity. Studies correlating row 1 position of needles and seeds and clinical outcomes after PB are lacking. Thus we undertook this analysis to demonstrate the safety and efficacy of our practice of positioning row 1 in patients during PB. We randomly selected 50 patients for this study who had a minimum 4 year follow-up from the 350 patients who have undergone I-125 PB at our institution. PB was performed with loose I-125 seeds to deliver a minimum peripheral dose of 144 Gy using a modified uniform loading technique. In all patients, row 1 on the template was positioned at a distance of 1-2 mm anterior to the posterior margin of the prostate gland from base to apex by angulating the rectal probe posteriorly to match the curvature of the prostate gland. Median patient age was 67 years, eight (16%) had diabetes, 12 (24%) were on blood thinners, one patient had ulcerative colitis. Patient records were evaluated for biochemical relapse free survival (RFS) and late rectal toxicity according to the RTOG criteria. Each patient's day 1 post-implant CT scan was reviewed for prostate quadrant dosimetry and various measures of rectal dosimetry including V100%, V100 Gy, rectal wall surface area dosimetry and seed number/distance from the rectal wall. After median follow-up of 63.5 months (range, 48-96 months) biochemical RFS was 100%. The median V100% of the anterior and posterior quadrants of the prostate was 91.8% and 90.9%, respectively. Median number of seeds < 5 mm, < 3 mm and < 1 mm from the rectal wall was 8 (0-26), 2 (0-17), and 0 (0-4), respectively. Median rectal V100% was 0.94 cc and rectal V100 Gy was 3.67 cc. Median rectal surface area receiving at least 100 Gy, 200 Gy and 100% of the prescription dose was 10.22 cm2, 0.80 cm2 and 4.88 cm2, respectively. The rate of RTOG grade 1 late rectal toxicity was 9/50 (18%). No patients had grade 2 or higher late toxicity. On multivariate analysis late grade 1 rectal toxicity was significantly associated with the presence of any seeds located < 5 mm from the anterior rectal wall (OR 1.19, p = 0.046) and the rectal surface area receiving at least 100 Gy (OR 1.32, p = 0.049). These results confirm the long-term safety and efficacy of implanting row 1 needles at a distance of 1-2 mm anterior to the posterior margin of the prostate gland during PB. This practice can provide good dosimetric coverage of the posterior peripheral zone with excellent biochemical RFS and minimal rectal toxicity in spite of the localized delivery of high radiation doses to the anterior rectal wall.

Outcomes for APBI With Strut-Based Brachytherapy: 101 Patients at 4.5 Years Median Follow-up

The SAVI Collaborative Research Group (SCRG), was created to study the long-term outcomes of women receiving accelerated partial breast irradiation (APBI) using strut-based applicators. The outcomes for the most mature subgroup of this study's patients (n = 101), accrued 3.5 to 6 years ago at 3 institutions, is presented. All patients were treated at least 42 months prior to abstract submission. Median follow-up of this cohort was 54 months. Patients were treated with APBI using the strut-based brachytherapy device with conventional dose and fractionation (3.4 Gy x 10 fx, BID). Treatment planning goals for the planning target volume were a V90 >90%, V150 <50 cc, and V200 <20 cc. Patients were followed regularly and outcome was graded based on the CTCAE v3.0 (common terminology criteria for adverse events, version 3.0). Seventy-one patients had invasive disease and 29 had ductal carcinoma in situ. The median age was 62 years (range, 40-82 years), with 82% post-menopausal. Median tumor size was 12.5 mm (range, 2-35 mm) with 92% being estrogen receptor positive. All patients completed APBI as planned with no serious adverse events. All patients met the dosimetric criteria with median V90 of 96%, V150 of 29 cc and V200 of 14 cc. Late toxicity (grade ≥2) rates were low; hyperpigmentation (0%), telangiectasias (2%), seroma (2%), fat necrosis (0%) and breast asymmetry secondary to radiation effects (3%). Statistically, tumor size had a weak association with fibrosis (21.7 cc vs 12.5 cc, p = 0.049) and surgical breast asymmetry (22 cc vs 12.7 cc, p = 0.089). There were no statistical associations (p < 0.05) between treatment parameters and toxicity, possibly due to the low event rates (≤3%). Local control was excellent with a true recurrence/marginal miss rate of 2% and an ipsilateral/elsewhere recurrence rate of 2%. These data will be updated and presented for 5 year median follow-up in October 2013. For these 101 patients with a median 4.5 years of follow-up (all with >3.5 years), strut-based brachytherapy appears to be a well-tolerated, effective treatment with low rates (<5%) of toxicities. With APBI an acceptable treatment for many women with early-stage breast cancer, strut-based brachytherapy continues on longer follow-up to be versatile, safe and effective.

Pilot study of proton therapy for treatment of regional lymphatics in patients with breast cancer.

100 Background: To determine the feasibility of proton therapy (PT) for regional nodal irradiation (RNI) in women with breast cancer and to compare target coverage and normal tissue avoidance between PT and conventional radiation. Methods: From May 2012 to May 2013, 14 women were prospectively enrolled in this pilot study; 5 had right-sided and 9 had left-sided. Median age at the time of PT was 53.7 years (range 37-73). The breast or chest wall and supraclavicular, axillary, and internal mammary (IM) lymph nodes were treated in all patients. Proton and conventional plans were developed for each patient; the superior plan, as defined by organ at risk sparing and target coverage, was treated. Targets and normal tissues were delineated on treatment CT scans. Wilcoxon signed rank sum test was used to compare dose-volume parameters. Results: For all 14 patients, the proton plan better met the dosimetric goals, and was used for treatment delivery. Median heart V5 measured 0.8% for the proton plans versus 23% for the conventional plans (p=0.0005). Median mean heart dose measured 0.55 Gy (range 0– 3.2Gy) for the proton plans versus 4.9 Gy (range 2-9.1 Gy) for the conventional plans (p=0.0005). Significant difference in median lung V5 and median V20 were found: 41% and 24% for the proton plans and 67% and 38% for conventional plans, respectively. PTV breast/chest wall coverage was adequate with both plans. Coverage of the level II axilla was higher in the proton plans (D95 48 Gy vs 44 Gy, p=0.01) as was coverage of the IM nodes (D95 50 Gy vs 46 Gy, p=0.01). Acute toxicity data is available for 12 patients. The most common acute toxicity was radiation dermatitis, with 9 patients experiencing grade 2 and 3 patients experiencing grade 3 toxicity. Other grade 2 toxicities included fatigue (n=3), pain (n=2), esophagitis (n=4), and skin infection (n=1). Radiation dermatitis was the only grade 3 toxicity. No grade 4 or 5 toxicities developed. Conclusions: Adjuvant PT is a well-tolerated, technically feasible modality for RNI, with a significant decrease in cardiac V5, V20, and mean heart dose as well as lung V5 and V20. Further investigation of PT for RNI in breast cancer is warranted to improve the therapeutic ratio by decreasing radiation exposure to the heart and lung. Clinical trial information: NCT01365845.

Clinical outcomes of high-dose-rate interstitial gynecologic brachytherapy using real-time CT guidance

To evaluate clinical outcomes of CT-guided high-dose-rate (HDR) interstitial brachytherapy for primary and recurrent gynecologic cancer. Records were reviewed for 68 women (34 with primary disease and 34 with recurrence) treated with CT-guided HDR interstitial brachytherapy between May 2005 and September 2011. Interstitial application was performed under general anesthesia using an iterative approach of catheter insertion and adjustment with serial image acquisition by CT in a dedicated brachytherapy suite. The median fractional brachytherapy dose was 3.9Gy delivered twice daily in seven fractions. The median cumulative dose in equivalent 2-Gy fractions was 74.8Gy. Actuarial survival estimates were calculated using the Kaplan-Meier method, and toxicity was reported by Common Toxicity Criteria. Primary disease sites were endometrial (34), cervical (17), vaginal (11), ovarian (3), and vulvar (3). Median age was 61.5 years, and tumor size at diagnosis was 3.4cm. Median D90 and V100 were 73.6Gy and 87.5%, respectively; median D2cc for bladder, rectum, and sigmoid were 67.1, 64.6, and 53.7Gy, respectively. With a median followup of 17 months, actuarial rates of local control, progression-free survival, and overall survival at 2 years for all patients were 86%, 60%, and 64%, respectively. There were 9 grade 3 late toxicities (six gastrointestinal and three vulvovaginal). HDR interstitial brachytherapy with CT-guided catheter placement results in acceptable local control, toxicity, and survival rates for women with primary or recurrent gynecologic cancer. Durable pelvic control may be achieved in most patients with this specialized brachytherapy technique.

Permanent Prostate Brachytherapy in Patients with Small Prostate Gland

generally at 6 months, and then every year. The endpoints were ‘‘biochemical failure’’ (‘‘BF’’, Phoenix), death from any cause (overall survival, OS) and death from PCa (PCa-specific survival, PCSS). Univariate and multivariable analysis (STATA 12) was used to identify factors associated with BF-free survival (BFFS) and 2-sided significance testing with P!0.05 considered statistically significant. Results: The median age of 582 implanted men was 62 years (yr): 86% had cT2a or less; the median PSAwas 5.6 ng/mL (4%O10); 19% had Gleason score 7; and 74% had low-risk (LR), with the remainder intermediate-risk disease (IR). Cytoreductive androgen deprivation was used in 13% for a median period of 180 days. The median D90 was 148 Gy (interquartile range 131-158 Gy), and the median V100%, V150%, and V200% were 90%, 49%, and 20% respectively. There was no perioperative mortality. The mean PSA after implant showed the ‘‘bounce’’ peak at 2 yr; by 5 yr, 84% of all men had PSA of !0.5 ng/mL; by 8 yr this proportion was 88%. The median PSA at last FU of men without BF was 0.1 ng/mL; 81% of last PSA measurements were #0.40 ng/mL and 66% #0.2 ng/mL. The median FUwas 6.0 yr. BF occurred in 36 men; 13 have commenced AD salvage. Bone metastases occurred in ten men. There were 28 deaths, five from prostate cancer; the other 23 from unrelated causes. The 5and 8-yr OS’s were 97% and 94%. The estimated PCSS’s and BFFS’s at the same times were 99.6% and 95%, and 99.6% and 91%, respectively. For men with LR disease, the 5and 8-yr BFFS’s were 95% and 92%. For IR men, they were 95% and 82%, respectively (P50.2027).

Clinical outcomes of patients with tumor bed-to-skin distance (TBS) ≤ 7 mm treated with accelerated partial breast irradiation (APBI) using multilumen catheter.

182 Background: The initial single-lumen Mammosite trial has shown that skin spacing had an important implication on cosmetic outcomes. In this study, we reviewed the patients who were treated with APBI using multilumen catheter and assessed the outcomes for patients with minimal TBS of ≤ 7mm. Methods: Between August 2008 and April 2011, 79 patients were treated with breast-conserving therapy and adjuvant APBI using the Contura Multi-Lumen balloon or strut-adjusted volume implant (SAVI) device. All patients received 3,400 cGy in 10 fractions delivered twice daily using high dose rate radiation with Iridium 192. The dose was prescribed to 1 cm from the applicator surface. Thirty-six patients had a TBS of ≤ 7mm. We analyzed the clinical outcomes according to RTOG 9517 and skin toxicities as per RTOG 9804 in this patient subgroup. Results: The median age was 65 years (range, 50-86 years). All patients had Tis-T1N0 carcinomas; 39% had DCIS and the rest had invasive carcinoma. The majority (92%) were treated with Contura Multi-Lumen balloon and 8% with SAVI. Median follow-up was 18 months (range 6-42 months). The average TBS was 4.8 mm (range 1-7). 21 patients (57%) had a TBS of ≤ 5mm. The median maximal skin dose was 116% (range 82-134%). The median V90, V95 and V100 were 98%, 96% and 92% respectively. The average V150 and V200 were 31.2 and 9.6 cc respectively. At a median of 3 weeks after treatment, 95% of the patients had good to excellent cosmetic outcome. 54% had grade 1, 21% patients had grade 2 skin toxicity and 25% did not have any skin reaction. At last follow-up, 82% of the patients did not have any residual late skin reaction. Grade 1 skin toxicity was reported in 13%, and grade 2 in 1 patient. Cosmesis was excellent in 72% and good in 28% of the patients. There was no loco-regional recurrence. Conclusions: In our patient population, APBI proved to be an effective treatment with a good to excellent cosmetic outcome and acceptable toxicity. Further investigation with larger patient populations and longer follow-up is warranted to confirm the safety and efficacy of APBI for patients with small TBS.

Results from the Quality Research in Radiation Oncology (QRRO) survey: Evaluation of dosimetric outcomes for low-dose-rate prostate brachytherapy

We report on quality of dose delivery to target and normal tissues from low-dose-rate prostate brachytherapy using postimplantation dosimetric evaluations from a random sample of U.S. patients. Nonmetastatic prostate cancer patients treated with external beam radiotherapy or brachytherapy in 2007 were randomly sampled from radiation oncology facilities nationwide. Of 414 prostate cancer cases from 45 institutions, 86 received low-dose-rate brachytherapy. We collected the 30-day postimplantation CT images of these patients and 10 test cases from two other institutions. Scans were downloaded into a treatment planning system and prostate/rectal contours were redrawn. Dosimetric outcomes were reanalyzed and compared with calculated outcomes from treating institutions. Median prostate volume was 33.4cm(3). Reevaluated median V(100), D(90), and V(150) were 91.1% (range, 45.5-99.8%), 101.7% (range, 59.6-145.9%), and 53.9% (range, 15.7-88.4%), respectively. Low gland coverage included 27 patients (39%) with a D(90) lower than 100% of the prescription dose (PD), 12 of whom (17% of the entire group) had a D(90) lower than 80% of PD. There was no correlation between D(90) coverage and prostate volume, number of seeds, or implanted activity. The median V(100) for the rectum was 0.3cm(3) (range, 0-4.3cm(3)). No outcome differences were observed according to the institutional strata. Concordance between reported and reevaluated D(90) values (defined as within ±10%) was observed in 44 of 69 cases. Central review of postimplantation CT scans to assess the quality of prostate brachytherapy is feasible. Most patients achieved excellent dosimetric outcomes, yet 17% had less than optimal target coverage by the PD. There was concordance between submitted target-coverage parameters and central dosimetric review in 64% of implants. These findings will require further validation in a larger cohort of patients.

Comparison of dose-volume analysis between standard Manchester plan and magnetic resonance image-based plan of intracavitary brachytherapy for uterine cervical cancer

To investigate the feasibility of image-based intracavitary brachytherapy (IBICBT) for uterine cervical cancer, we evaluated the dose–volume histograms (DVHs) for the tumor and organs at risk (OARs) and compared results from the IBICBT plan and the standard Manchester system (Manchester plan) in eight patients as a simulation experiment. We performed magnetic resonance imaging (MRI) and computed tomography (CT) following MRI-adapted applicator insertion, then superimposed MR images on the planning CT images to describe the contours of high-risk clinical target volume (HR CTV) and OARs. The median volume of HR CTV was 29 cm3 (range, 21–61 cm3). Median D90 (HR CTV) and V100 (HR CTV) were 116.1% prescribed doses (PD) (90.0–150.8%) and 96.7% (84.2–100%), respectively, for the Manchester plan. In comparison, we confirmed that the median D90 (HR CTV) was 100% PD in the IBICBT plan for all patients. Mean D2cc (bladder) was 101.8% PD for the Manchester plan and 83.2% PD for the IBICBT plan. Mean D2cc (rectum) was 80.1% PD for the Manchester plan and 64.2% PD for the IBICBT plan. Mean D2cc (sigmoid) was 75% PD for the Manchester plan and 57.5% PD for the IBICBT plan. One patient with a large tumor (HR CTV, 61 cm3) showed lower D90 (HR CTV) with the Manchester plan than with the IBICBT plan. The Manchester plan may represent overtreatment for small tumors but insufficient dose distribution for larger tumors. The IBICBT plan could reduce OAR dosage while maintaining adequate tumor coverage.

Interstitial preoperative high-dose-rate brachytherapy for early stage cervical cancer: Dose–volume histogram parameters, pathologic response and early clinical outcome

To analyze dose-volume histogram parameters and pathologic response after preoperative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs). From June 2007 to December 2011, 32 patients with a histologically proven invasive cervical cancer with high risk of local recurrence (size >2cm, adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB. With a median clinical target volume of 50cc (minimum-maximum, 42-74), the median V100 was 49cc (minimum-maximum, 42-50). Median D90 was 45Gy (equivalent dose at 2Gy per fraction, 56Gyαβ10). Median D2cc was 34Gy, 31Gy, 28Gy, and 38Gyαβ3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histologic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median followup of 24 months (minimum-maximum, 5-48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2-G3 toxicities were noticed. Preoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Dose-volume histogram parameters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs.

Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum.

On the feasibility of treating to a 1.5 cm PTV with a commercial single-entry hybrid applicator in APBI breast brachytherapy

PurposeTo evaluate and determine whether 30 patients previously treated with the SAVI™ device could have been treated to a PTV_EVAL created with a 1.5 cm expansion. This determination was based upon dosimetric parameters derived from current recommendations and dose-response data.Material and methodsThirty patients were retrospectively planned with PTV_EVALs generated with a 1.5 cm expansion (PTV_EVAL_1.5). Plans were evaluated based on PTV_EVAL_1.5 coverage (V90, V95, V100), skin and rib maximum doses (0.1 cc maximum dose as a percentage of prescription dose), as well as V150 and V200 for the PTV_EVAL_1.5. The treatment planning goal was to deliver ≥90% of the prescribed dose to ≥90% of the PTV_EVAL_1.5. Skin and rib maximum doses were to be ≤125% of the prescription dose and preferably ≤100% of the prescription dose. V150 and V200 were not allowed to exceed 52.5 cc and 21 cc, respectively. Plans not meeting the above criteria were recomputed with a 1.25 cm expanded PTV_EVAL and re-evaluated.ResultsBased on the above dose constraints, 30% (9/30) of the patients evaluated could have been treated with a 1.5 cm PTV_EVAL. The breakdown of cases successfully achieving the above dose constraints by applicator was: 0/4 (0%) 6-1, 6/15 (40%) 8-1, and 3/11 (27%) 10-1. For these PTV_EVAL_1.5 plans, median V90% was 90.3%, whereas the maximum skin and rib doses were all less than 115.2% and 117.6%, respectively. The median V150 and V200 volumes were 39.2 cc and 19.3, respectively. The treated PTV_EVAL_1.5 was greater in volume than the PTV_EVAL by 41.7 cc, and 60 cc for the 8-1, and 10-1 applicators, respectively. All remaining plans (17) successfully met the above dose constraints to be treated with a 1.25 cm PTV_EVAL (PTV_EVAL_1.25). For the PTV_EVAL_1.25 plans, V90% was 93.7%, and the maximum skin and rib doses were all less than 109.2% and 102.5%, respectively. The median V150 and V200 volumes were 41.2 cc and 19.3, respectively. The treated PTV_EVAL_1.25 was greater in volume than the PTV_EVAL by 16 cc, 24.9 cc, and 33.5 cc for the 6-1, 8-1 and 10-1 applicators, respectively.ConclusionsIt is dosimetrically possible to treat beyond the currently advised 1.0 cm expanded PTV_EVAL. Most patients should be able to be treated with a 1.25 cm PTV_EVAL and a select group with a 1.5 cm PTV_EVAL. Applicator size appears to determine the ability to expand to a 1.5 cm PTV_EVAL, as smaller devices were not as propitious in this regard. Further studies may identify additional patient groups that would benefit from this approach.