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PurposeWe report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up.Methods and materialsEligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen

Author(s): Hsu, I-Chow; Rodgers, Joseph P; Shinohara, Katsuto; Purdy, James; Michalski, Jeff; Roach, Mack; Vigneault, Eric; Ivker, Robert A; Pryzant, Rodger M; Kuettel, Michael; Taussky, Daniel; Gustafson, Gary S; Raben, Adam; Sandler, Howard M | Abstract: PurposeTo report the long-term outcome of patients with prostate cancer treated with external beam radiation therapy and high dose rate (HDR) brachytherapy from a prospective multi-institutional trial conducted by NRG Oncology/RTOG.Methods and materialsPatients with clinically localized (T1c-T3b) prostate cancer without prior history of transurethral resection of prostate or hip prosthesis were eligible for this study. All patients were treated with a combination of 45 Gy in 25 fractions from external beam radiation therapy and one HDR implant delivering 19 Gy in 2 fractions. Adverse events (AE) were collected using Common Toxicity Criteria for Adverse Events, version 3. Cumulative incidence was used to estimate time to severe late gastrointestinal (GI)/genitourinary (GU) toxicity, biochemical failure, disease-specific mortality, local failure, and distant failure. Overall survival was estimated using the Kaplan-Meier method.ResultsOne hundred and twenty-nine patients were enrolled from July 2004 to May 2006. AE data was available for 115 patients. Patients were National Comprehensive Cancer Network (NCCN) intermediate to very high risk. The median age was 68, T1c-T2c 91%, T3a-T3b 9%, PSA ≤10 70%, PSA g10 to ≤20 30%, GS 6 10%, GS 7 72%, and GS 8 to 10 18%. Forty-three percent of patients received hormonal therapy. At a median follow-up time of 10 years, there were 6 (5%) patients with grade 3 GI and GU treatment-related AEs, and no late grade 4 to 5 GI and GU AEs. At 5 and 10 years, the rate of late grade 3ngastrointestinal and genitourinary AEs was 4% and 5%, respectively. Five- and 10-year overall survival rates were 95% and 76%. Biochemical failure rates per Phoenix definition at 5 and 10 years were 14% and 23%. The 10-year rate of disease-specific mortality was 6%. At 5 and 10 years, the rates of distant failure were 4% and 8%, respectively. The rates of local failure at 5 and 10 years were 2% at both time points.ConclusionsCombined modality treatment using HDR prostate brachytherapy leads to excellent long-term clinical outcomes in this prospective multi-institutional trial.

Purpose/Objective(s) Androgen suppression can improve outcomes when added to radiotherapy (RT) for intermediate risk prostate cancer, but no study to date has reported its utility in the context of contemporary, dose-escalated RT. Herein, the clinical outcomes of a phase III prospective trial evaluating the utility of total androgen suppression (TAS) combined with dose-escalated RT for patients with intermediate risk prostate cancer are reported. Materials/Methods Eligible patients had intermediate risk prostate cancer defined as harboring ≥ 1 of the following risk factors: clinical stage T2b-T2c, Gleason score 7, or PSA value > 10 and ≤ 20 ng/mL. Patients with all three risk factors and ≥ 50% of biopsy cores positive were ineligible. After stratification by number of intermediate risk factors (single vs. multiple), RT boost modality, and baseline comorbidity (ACE-27 comorbidity index ≥ vs. Results The study completed its accrual objective. Between 2009 and 2016, 1538 patients were randomized. There were 750 eligible patients on Arm 1 and 742 on Arm 2 comprising the modified intent-to-treat population. 67% had a single intermediate risk factor. 88% were treated with EBRT with the remainder receiving EBRT plus brachytherapy boost. 33% had an ACE-27 score ≥ grade 2. With a median follow up of 6.2 years, 219 deaths occurred, 119 in Arm 1 and 100 in Arm 2, yielding 5-year overall survival estimates of 90% vs. 91%, respectively [HR 0.85 (95% CI 0.65-1.11); P = 0.22]. 193 patients experienced PSA failure, 125 in Arm 1 and 68 in Arm 2 [HR 0.52 (0.39-0.70); P Conclusion While the addition of TAS to dose-escalated RT did not improve overall survival for men with intermediate risk prostate cancer, significant improvements in rates of metastases, deaths due to prostate cancer, and PSA failures support the continued use of combination dose-escalated RT and TAS. Benefits will need to be weighed against the increased risk of adverse events and the patient reported outcomes analysis.

Objectives: We reviewed testosterone changes for patients who were treated with radiation therapy (RT) alone on NRG oncology RTOG 9408. Methods and materials: Patients (T1b-T2b, prostate-specific antigen

Purpose To report the biochemical control rate and clinical outcomes with real-time inverse planning (inverse optimization prostate seed implant [IO-PSI]) for favorable-risk (FR) and intermediate-risk (IR) prostate adenocarcinoma in a community practice setting. This analysis is an extended followup of our initial report, with favorable early biochemical control rate (biochemical nonevidence of disease) of 97% at 4 years. Methods and Materials Three hundred fifty-seven evaluable patients with FR and IR prostate cancer underwent real-time IO-PSI (iodine-125/145 Gy or palladium-103/120 Gy) between 2001 and 2013. Results With a median followup of 54 months (range, 24–110 months), the absolute biochemical failure free survival of disease was 96%. The 8-year actuarial probability of prostate-specific antigen failure-free survival for FR and IR cohorts was 92.4% and 87%, respectively. Late genitourinary and gastrointestinal toxicity remained low. Late Grade 2 and Grade 3 genitourinary toxicity was 19% and 1%, respectively. Late Grade 2 and 3 rectal bleeding rates were 1% and 0%, respectively. No difference in biochemical control was observed with preimplant short course androgen deprivation or between Gleason score 3 + 4 vs. 4 + 3 patients. No dosimetric parameter was predictive of biochemical failure. Patients with FR had a significantly decreased risk of failure (hazard ratio = 0.26; 95% confidence interval = 0.09–0.78; p = 0.02) compared with those with IR. Patients with a prostate-specific antigen nadir >0.4 ng/mL had an increased risk of failure (hazard ratio = 1.37; 95% confidence interval = 1.27–1.47; p Conclusions Our initial biochemical and clinical outcomes using real-time IO-PSI persisted with extended followup and support our original hypothesis for use of a reduced number of sources, needles, and total activity, suggesting that with IO, less is more.

To evaluate the lung and pelvic seed migration and intraprostatic dose variability for prostate seed implant (PSI) using bio-absorbable polymer "coated" seeds for intraoperative planning.A total of 100 PSI patients were initially implanted with uncoated I-125 (STM 1251 or I125-SL, N = 85) or Pd-103 (mod 200, N = 15) seeds, and 105 PSI patients were implanted subsequently with coated seeds using inverse optimization with real-time planning. Implant technique, average number of needles, and dose objectives remained identical among the cohorts.Day 30 postimplant comparison of seed migration demonstrated a significant reduction in overall lung and pelvic seed migration from 25% (uncoated) to 4% (coated) (p 0.0001). A measurable reduction in intraprostatic dose variability was observed in patients with the coated seeds when comparing 30 days dosimetry results for V100, V150, and D90 for prostate, and V110 for the rectum. A statistically significant reduction in the standard deviation from Day 0 to Day 30 for the above parameters for the prostate as well as for V110 of rectum was also observed. A significant improvement in implant quality at Day 30 was demonstrated using Radiation Therapy Oncology Group (RTOG) evaluation criteria range with the coated seeds cohort.PSI using coated seeds shows lower lung and pelvic seed migration compared with those using uncoated seeds and compares favorably to pelvic stranded seed migration reports. A higher concordance was observed with less dose variability in dosimetric parameters on Day 30 dosimetry compared with that on Day 0. Improvement in the implant quality was also observed using the RTOG criteria, suggesting reduced intraprostatic migration.

To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival.Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment.The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to.0001).The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival.

Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique.Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition.Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup.IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

Comparison of inverse optimization (IO) to modified peripheral (MP) and geometric optimization (GO) intraoperative computer planning options for permanent seed implantation (PSI) of the prostate.One hundred ten patients underwent PSI with iodine-125. Three computer planning options were compared including MP loading, GO, and IO. Preimplant dose goals (prescribed dose [PD] of 144 Gy) and normal tissue constraints were determined at the outset by the participating physicians before intraoperative computer planning. A single computer planning system was used for this comparison. Postimplant dosimetry was performed at 4-5 weeks and compared for V(100) and D(90), urethral V(150), and rectal V(110) of the PD. Acute urinary morbidity was evaluated and compared.All three options achieved a similar preimplant median V(100) (97%). The median number of needles and seeds implanted was greater with GO (29, 75) compared to MP (16, 66) and IO (17, 66) (p0.0001 and p=0.0024, respectively). Postimplant dosimetry showed that IO achieved a higher percentage with V(100)95% of the PD in multivariate analysis (p=0.04) and a lower percentage postimplant D(90)140 Gy (7%) than for MP/GO (26%) (p = 0.01). IO predicted for lower urethral dose (p=0.0169), despite a higher median D(90) (169 Gy) than either MP (159 Gy) or GO (151 Gy) (p = 0.0025). The median percentage V(150) urethra for IO was 8% vs. 16% for MP and 23% for GO (p = 0.0005). With a median followup time of 6 months, acute Grade 2 urinary symptoms were higher with GO (81%) vs. MP (36%) and IO (53%) (p = 0.0019).Dosimetric outcomes for IO compare favorably to either MP or GO when performed in real time for PSI. In contrast to GO, IO and MP demonstrated excellent correlation between the intraoperative and postoperative plans while using fewer total and interior placed needles and seeds. IO appears feasible as an alternative intraoperative planning solution for PSI.

Purpose: To determine whether a computer-assisted target volume delineation (CAT) system using a deformable image registration approach can reduce the variation of target delineation among physicians with different head and neck (HN) IMRT experiences and reduce the time spent on the contouring process. Materials and Methods: We developed a deformable image registration method for mapping contours from a template case to a patient case with a similar tumor manifestation but different body configuration. Eight radiation oncologists with varying levels of clinical experience in HN IMRT performed target delineation on two HN cases, one with base-of-tongue (BOT) cancer and another with nasopharyngeal cancer (NPC), by first contouring from scratch and then by modifying the contours deformed by the CAT system. The gross target volumes were provided. Regions of interest for comparison included the clinical target volumes (CTVs) and normal organs. The volumetric and geometric variation of these regions of interest and the time spent on contouring were analyzed. Results: We found that the variation in delineating CTVs from scratch among the physicians was significant, and that using the CAT system reduced volumetric variation and improved geometric consistency in both BOT and NPC cases. The average timesaving when using the CAT system was 26% to 29% for more experienced physicians and 38% to 47% for the less experienced ones. Conclusions: A computer-assisted target volume delineation approach, using a deformable image-registration method with template contours, was able to reduce the variation among physicians with different experiences in HN IMRT while saving contouring time.

To compare dosimetric outcomes between two real-time prostate seed implantation (PSI) techniques to evaluate the impact of three-dimensional (3D) intraoperative computer planning on target coverage, conformality, and preset urethral and rectal dose constraints.One hundred and fourteen patients with clinically localized prostate cancer underwent ultrasound-guided transperineal PSI of the prostate with (125)I sources as monotherapy. From 1999 to 2001, 69 patients were implanted in real-time using a standard look-up nomogram (Group 1: NG-PSI). All patients were implanted with a modified peripheral loading technique in which 75-80% of the calculated total activity was delivered to the gland periphery, with the remaining 20-25% activity placed in the gland interior, to achieve a prescribed dose (PD) of 144 Gy to cover the gland with acceptable homogeneity. No preoperative or intraoperative planning was performed to set dose constraints to the urethra or anterior rectal wall. Dosimetric outcome from this group was compared with 45 patients subsequently implanted after 2001 using an intraoperative 3D computer planning system (Group 2: 3D-PSI). A similar modified peripheral loading technique was used as an option in the planning system. Preoperative dose constraints were placed on the urethra (V15035%), prostate (V10095% of PD; D90: 140-180 Gy), and rectal wall (V1101.5 cc) with real-time dosimetric feedback performed after peripheral loading. Manual dose optimization was performed to determine interior needle position and remaining number and placement of (125)I sources to adhere to urethral and rectal constraints and target coverage goals. Both groups underwent postimplant CT analysis to determine dosimetric outcome with regard toV100(prostate), D90(prostate), V150(urethra), and V110(rectum). Univariate and multivariate analysis was performed to determine variables impacting on dosimetric outcome.Analysis of preimplant and postimplant variables demonstrated no difference in the median preimplant gland volume (33 cc vs. 35 cc; p = 0.31), median mCi/seed strengths (0.4 vs. 0.45 mCi; p = 0.23), median V100 (94% vs. 94%), or median D90 at postimplant Day 30 (165 Gy vs. 160 Gy; p = 0.26) between Groups 1 and 2. However, for Group 2 (3D-PSI) the median total mCi implanted (26 vs. 33 mCi; p0.0001) and the median number of seeds implanted (67 vs. 83; p0.0001) were reduced substantially. The percent of patients exceeding a D90180 Gy was reduced from 29% in Group 1 to 16% in Group 2 (p = 0.08). A reduction was observed in the percent of patients receiving a D90140 Gy (14% Group 1 vs. 9% Group 2, p = 0.56). The median V150(urethra) for Group 2 was reduced dramatically with 3D-PSI compared with NG-PSI (63% vs. 17%; p0.0001). A V150(urethra)30% was observed in 88% in Group 1 compared with 29% in Group 2, p0.0001. Similarly, the median V110(rectum) for Group 1 was significantly higher than that in Group 2 (1.93 vs. 0.26 cc; p0.0001). The percent of patients with V110(rectum)1.5 cc in Group 1 and Group 2 was 57% and 13%, respectively (p0.0001).The adoption of 3D computer intraoperative dose planning and optimization for prostate seed implantation resulted in dramatic reductions in urethral and rectal wall doses, while consistently producing excellent target coverage with reduced dose variability above 180 Gy and below 140 Gy, compared with the use of a standard look-up nomogram. Additionally, the reduction in total mCi and number of seeds needed to achieve improved conformality was substantial and may have implications for cost savings.

A multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) program was implemented successfully at Monmouth Medical Center, a community hospital at Long Branch, New Jersey. Our clinical experience gained in the treatment of over 80 patients using IMRT for prostate, head and neck, and brain is reviewed, and some of the clinical issues are also, discussed. Implementation of the IMRT requires a treatment planning system, computer-controlled beam-shaping aperture, electronic record and verify system, and a good physics quality assurance program. These components, by grouping them efficiently, have created a seamless workflow for our complete radiotherapy process of IMRT. Each of these radiotherapy processes are discussed for clarity and the clinical importance is also evaluated. Of particular interest is inverse treatment planning that will impact treatment delivery such as beam orientation, treatment ports, and organ motion of IMRT. A checklist for physics and departmental quality assurance is suggested, with the intention of providing systematic workflow, making IMRT feasible at a community medical center setting. This is especially important because most of our cancer patients received radiation therapy locally. Lastly, the reimbursement issue affecting the implementation of IMRT at our medical center is also discussed to justify this new treatment protocol for future clinical outcomes.

Purpose/Objective: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features—deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. Methods and Materials: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1–2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2–0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. Results: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (± 0.9) mm and inter breath-hold reproducibility of 2.5 (± 1.6) mm, as determined from diaphragm position. Patients were able to perform 10–13 breath-holds in one session, with a comfortable breath-hold duration of 12–16 s. Conclusion: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Purpose : Local failure is a major obstacle to the cure of locally advanced non small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially representing an enhancement of the therapeutic ratio of radiation therapy for lung cancer. We performed this analysis of 45 non-small cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of computer derived lung dose volume histograms to predict serious pulmonary toxicity, to assess the feasibility of this approach, and to examine the resulting survival. Methods : There were 28 males (62%) and 17 females (38%). The median age was 65 (range: 38–82). Tumor stage was Stage I/II in 13%, IIIa in 42%, and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and other non-small cell histologies in the others. Only 47% of patients, had combined favorable prognostic factors (i.e. KPS ≤ 80, and ≤5% wt. loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2–72 Gy) delivered in fractions of 1.8 Gy, 5 days per week. Results : Seven patients did not complete 3-DCRT due to disease progression outside the port. Follow-up data are mature: the median follow up of the 6 survivors is 43.5 months (35–59). Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7 months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity ≥grade 3 occurred in 9% of patients. Dose volume histograms were available in 31 patients and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (38) of patients with > 30% of lung volume receiving ≥25 Gy, versus 4% (123) of patients with ≤30% lung receiving ≥25 Gy ( P = 0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (414) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% ( P = 0.03). Conclusions : Despite adverse prognostic criteria median survival is encouraging and may be higher than some combined modality approaches. Dose volume histogram parameters may be useful to determine the maximum dose for individual patients and thereby permit avoidance of toxicity.

Purpose: The purpose of this study was to assess the feasibility of 103 Pd bracytherapy in the management of primary unresectable carcinoma of the pancreas. Methods and Materials: Between August 1988 and January 1992, 11 patients with biopsy-proven primary unresectable adenocarcinoma of the pancreas were treated with 103 Pd brachytherapy during laparotomy. The median age was 66 (range 57–70). The most common presenting symptoms were weight loss (eight patients), pain (six patients), and nausea/vomiting (four patients). Less common symptoms were jaundice (two patients), early satiety (two patients), and ascites (one patient). All patient underwent laparotomy and surgical staging. Eight patients had T3N0M0 disease, two patients had T3N1M0 disease, and one patient had T3N1M1 disease. The surgical procedure performed was biliary bypass in six patients, biopsy only in four patients, and gastric bypass in one patient. The average tumor dimension was 4.0 cm. The median activity, matched peripheral dose (MPD) and implanted volumes were 95.3 mCi, 124.4 Gy, and 33 cm 3 , respectively. The median initial dose rate was 0.21 Gy per hour. Five patients received postoperative external beam radiation therapy (median 45 Gy) and seven patients received chemotherapy postoperatively. The median follow-up was 7 months (range 1–19). Results: The median survival for the entire group of patients was 6.9 months. Ten of 11 patients have died, with 1 patient presently alive and receiving chemotherapy for metastatic disease to the liver, but without local progression radiographically. Five of 11 patients (45%) were locally controlled, defined as either a complete response or freedom from progression at the site of the implant as evaluated by computed tomography scan. In the other six patients, the median time to local progression was 6.9 months. Five patients developed distant metastases (four liver, one subcutaneous nodule). Two patients failed in regional sites (one omentum, one paraaortic lymph node). Four of 11 patients (36%) developed acute postoperative complications that included one gastric outlet obstruction, one duodenal perforation, and two with sepsis. One of 11 patients (9%) developed a late complication of radiation enteritis 5 months after implantation. The median survival for patients experiencing complications was 1.7 months as compared to 8.4 months for the patients who did not develop a complication ( p = 0.10). Pain relief was obtained in five out of six (83%) for the patients presenting with pain for a median duration of 24 weeks. Local control did not appear to be related to the MPD, dose rate, implanted volume, treatment with external beam irradiation, or the use of chemotherapy. Patients were more likely to develop a complication if the MPD was greater than 115 Gy (four out of six patients) as compared to those whose MPD was less than 115 Gy (one out of five patients) p = 0.12). Conclusions: Because there was no improvement in median survival over conventional modalities, and the complication rate was high; we do not recommend 103 Pd brachytherapy as a component of the treatment of unresectable adenocarcinoma of the pancreas.

Purpose To review the outcomes of a prospective management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion. Methods and Materials Between August 2003 and June 2007, 20 patients who presented with squamous cell carcinoma of the tonsil, without involvement of the base of the tongue or midline soft palate, and with Stage N1-N2b disease were prospectively treated with radiotherapy to the primary site and ipsilateral neck. In addition, 18 patients received concurrent chemotherapy. The actuarial freedom from contralateral nodal and in-field progression was determined. Acute and late toxicity were prospectively evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, and Radiation Therapy Oncology Group criteria. Results The nodal disease was Stage N1 in 4 patients, N2a in 3 patients, and N2b in 13 patients. At a median follow-up 19 months (range, 12–40), no in-field or contralateral nodal recurrences had been observed. The 2-year freedom from distant metastasis rate was 87.4%. The actuarial 2-year disease-free and overall survival rates were both 79.5%. Late Radiation Therapy Oncology Group grade 2 xerostomia occurred in 1 patient (5%). No late Grade 3 or greater toxicity was observed. No patient was feeding tube dependent at their last follow-up visit. Conclusion In carefully selected patients with node-positive, lateralized tonsillar cancer, treatment of the ipsilateral neck and primary site does not appear to increase the risk of contralateral nodal failure and reduces late morbidity compared with historical controls. Although the outcomes with ipsilateral radiotherapy in the present series were promising, these findings require longer follow-up and validation in a larger patient cohort.

Purpose To perform an independent validation of an anatomy-based inverse planning simulated annealing (IPSA) algorithm in obtaining superior target coverage and reducing the dose to the organs at risk. Method and Materials In a recent prostate high-dose-rate brachytherapy protocol study by the Radiation Therapy Oncology Group (0321), our institution treated 20 patients between June 1, 2005 and November 30, 2006. These patients had received a high-dose-rate boost dose of 19 Gy to the prostate, in addition to an external beam radiotherapy dose of 45 Gy with intensity-modulated radiotherapy. Three-dimensional dosimetry was obtained for the following optimization schemes in the Plato Brachytherapy Planning System, version 14.3.2, using the same dose constraints for all the patients treated during this period: anatomy-based IPSA optimization, geometric optimization, and dose point optimization. Dose–volume histograms were generated for the planning target volume and organs at risk for each optimization method, from which the volume receiving at least 75% of the dose (V 75% ) for the rectum and bladder, volume receiving at least 125% of the dose (V 125% ) for the urethra, and total volume receiving the reference dose (V 100% ) and volume receiving 150% of the dose (V 150% ) for the planning target volume were determined. The dose homogeneity index and conformal index for the planning target volume for each optimization technique were compared. Results Despite suboptimal needle position in some implants, the IPSA algorithm was able to comply with the tight Radiation Therapy Oncology Group dose constraints for 90% of the patients in this study. In contrast, the compliance was only 30% for dose point optimization and only 5% for geometric optimization. Conclusions Anatomy-based IPSA optimization proved to be the superior technique and also the fastest for reducing the dose to the organs at risk without compromising the target coverage.

Purpose To report results of a phase II trial of high-dose-rate intra-operative radiation therapy (HDR-IORT) for malignant pleural mesothelioma (MPM). Methods and materials Seven patients had extrapleural pneumonectomy with IORT (EPP/IORT) and 6 patients had pleurectomy/decortication with IORT (PD/IORT) between 1994 and 1996. IORT was delivered with 192 Ir using a customized applicator with a remote afterloader. A median of 3 sites were treated to a median area of 143 cm 2 . A dose of 1500 cGy was prescribed at each site, with 1000 cGy delivered to the mediastinum. Postoperative external beam radiation therapy (EBRT) was given 3–5 weeks later. Median follow-up was 8 months (range, 1–84 months). Results Five patients developed local failure. Two-year local control and survival rates were 35% and 23%, respectively. Mortality was 2/13 (15%), 1 from each surgical group. Serious complications requiring further intervention occurred in 3/6 (50%) of the EPP/IORT group and 1/5 (20%) of the PD/IORT group. Conclusions HDR-IORT after EPP for MPM is prohibitively toxic and has been abandoned, while its use with PD remains in question.

Purpose The focus of this work is to develop a practical planning method that results in increased dose conformity and reduced treatment time for segmental multileaf collimation (sMLC) based intensity-modulated radiation therapy (IMRT) delivery. Methods and materials Additional regions for dose constraint are introduced within the normal tissue during the planning process by designing a series of concentric ellipsoids around the target. A dose gradient is then defined by assigning dose constraints to each concentric region. The technique was tested at two centers and data for 26 and 10 patients, respectively, are presented allowing for differences in treatment technique, beam energy, ellipsoid definition, and prescription dose. At both centers, a series of patients previously treated for prostate cancer with IMRT were selected, and comparisons were made between the original and new plans. Results While meeting target dose specifications and normal tissue constraints, the average number of beam directions decreased by 1.6 with a standard error (SE) of 0.1. The average time for delivery at center 1 decreased by 29.0% with an SE of 2.0%, decreasing from 17.5 min to 12.3 min. The average time for delivery at center 2 decreased by 29.9% with an SE of 3.8%, decreasing from 11 min to 7.7 min. The amount of nontarget tissue receiving D 100 decreased by 15.7% with an SE of 2.4%. Nontarget tissue receiving D 95 , D 90 , and D 50 decreased by 16.3, 15.1, and 19.5%, respectively, with SE values of approximately 2% at center 1. Corresponding values for D 100 , D 95 , D 90 , and D 50 decreased by 13.5, 16.7, 17.1, and 5.1%, respectively, with SE values of less than 3% at center 2. Conclusions By designating subsets of tissue as concentric regions around the target(s) and carefully defining each region's dose constraints, we have gained an increased measure of control over the region outside the target boundaries. This increased control manifests as two distinct endpoints that are beneficial to the IMRT process: increased dose conformity and decreased treatment time.

To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI).Between 1989-1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45-80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scoresor =7. The median pretreatment PSA was 7 ng/mL (range: 1-58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level wasor =10.0 ng/mL and Gleason scoreor = 6; those with one and two adverse prognostic features (PSA10 ng/mL and Gleason score6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12-126 months).Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA10 ng/mL and Gleason score6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0. 4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication.Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.

To evaluate the role of detailed pathologic features in predicting outcome for early-stage prostate cancer treated with I-125 brachytherapy. The pretreatment biopsy slides of 103 patients with T1/T2 and Gleason scores of 4–7 prostatic carcinoma, which was treated by transperineal I-125 implantation, were reviewed retrospectively by a single pathologist (P.B.G.). Biochemical tumor control rates [prostate-specific antigen (PSA) below 1.0] were correlated with pretreatment PSA, Gleason score, the amount of tumor in the biopsy samples, and the presence of perineural invasion.In Cox proportional-hazard, multivariate analysis, the strongest predictors of failure were pretreatment PSA above 10 ng/ml (P = 0.013) and the length of the biopsy specimen replaced by tumor (P = 0.15). The percent of biopsy tissue replaced by tumor (P = 0. 74), perineural invasion (P = 0.78), and Gleason score (P = 0.66) were less predictive of prognosis. It was concluded that pretreatment PSA is the strongest predictor of biochemical failure. Detailed assessment of pathological features on needle biopsy added little prognostic information beyond that of pretreatment PSA alone. Like all other prognostic parameters for prostate cancer, there is considerable overlap in pathologic features between those patients who will or will not be controlled biochemically. Radiat. Oncol. Invest. 6:170–174, 1998. © 1998 Wiley-Liss, Inc.

Purpose : Minimal literature exists with 10-year data on neck control in advanced head and neck cancer. The purpose of this study is to determine long-term regional control for base of tongue carcinoma patients treated with primary radiation therapy plus neck dissection. Methods and Materials : Between 1981–1996, primary radiation therapy was used to treat 68 patients with squamous cell carcinoma of the base of tongue. Neck dissection was added for those who presented with palpable lymph node metastases. The T-stage distribution was T1, 17; T2, 32; T3, 17; and T4, 2. The N-stage distribution was N0, 10; N1, 24; N2a, 6; N2b, 11, N2c, 8; N3, 7; and Nx, 2. Ages ranged from 35 to 77 (median 55 years) among the 59 males and nine females. Therapy generally consisted of initial external beam irradiation to the primary site (54 Gy) and neck (50 Gy). Clinically positive necks were boosted to 60 Gy with external beam irradiation. Three weeks later, the base of tongue was boosted with an Ir-192 interstitial implant (20–30 Gy). A neck dissection was done at the same anesthesia for those who presented with clinically positive necks, even if a complete clinical neck response was achieved with external beam irradiation. Neoadjuvant cisplatin-based chemotherapy was administered to nine patients who would have required a total laryngectomy if their primary tumors had been surgically managed. The median follow-up was 36 months with a ranged from 1 to 151 months. Eleven patients were followed for over 8 years. No patients were lost to follow-up. Results : Actuarial 5- and 10-year neck control was 96% overall, 86% after radiation alone, and 100 after radiation plus neck dissection. Pathologically negative neck specimens were observed in 70% of necks dissected after external beam irradiation. The remaining 30% of dissected necks were pathologically positive. These specimens contained multiple positive nodes in 83% despite a 56% overall complete clinical neck response rate to irradiation. Regional failure occurred in only two patients, neither of whom underwent adjuvant neck dissection. Symptomatic neck fibrosis (RTOG grade 3) was not observed. Actuarial 5- and 10-year local control was 88% and 88%, disease-free survival was 80% and 67%, and overall survival was 86% and 52%. Conclusion : For base of tongue cancer, most patients can obtain long-term regional control with no severe complications after definitive radiation therapy, plus neck dissection for those who present with lymphadenopathy. Complete clinical regression of palpable neck metastases after irradiation poorly correlates with pathologic outcome. Our current policy is to include neck dissection at the time of implantation for patients who present with palpable neck metastases. We realize that this therapeutic approach may overtreat some patients, but we are reluctant to change our policy in light of these excellent outcomes.