A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy.

PURPOSE: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. METHODS AND MATERIALS: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. RESULTS: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. CONCLUSIONS: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.

Long-term outcome comparison for standard fractionation (>59 Gy) versus hyperfractionated (>45 Gy) radiotherapy plus concurrent chemotherapy for limited-stage small-cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is commonly employed in limited-stage small-cell lung cancer (LS-SCLC); however, the optimal radiotherapy regimen is still unknown. This 3-institution analysis compares long-term disease control and survival outcomes for once- (QD) versus twice-daily (BID) radiotherapy at contemporary doses. METHODS AND MATERIALS: Data were collected for LS-SCLC patients treated with platinum-based CCRT and planned RT doses of >5940 cGy at >180 cGy QD or >4500 cGy at 150 cGy BID. Comparative outcome analyses were performed for treatment groups. RESULTS: From 2005 through 2014, 132 patients met inclusion criteria for analysis (80 QD, 52 BID). Treatment groups were well-balanced, excepting higher rate of advanced mediastinal staging, longer interval from biopsy to treatment initiation, and lower rate of prophylactic cranial irradiation for the QD group, as well as institutional practice variation. At median survivor follow-up of 33.5 months (range, 4.6-105.8), 80 patients experienced disease failure (44 QD, 36 BID), and 106 died (62 QD, 44 BID). No differences in disease control or survival were demonstrated between treatment groups. CONCLUSION: The present analysis did not detect a difference in disease control or survival outcomes for contemporary dose QD versus BID CCRT in LS-SCLC.

Comparing high-dose cisplatin with cisplatin-based combination chemotherapy in definitive concurrent chemoradiation setting for locally advanced head and neck squamous cell carcinoma (LAHNSCC).

BACKGROUND: High-dose cisplatin (Cis) is a preferred systemic agent for concurrent chemoradiation (CRT) in locally advanced head and neck squamous cell cancer (LAHNSCC) patients. As some patients are unable to tolerate Cis, this study compares the toxicity and efficacy of weekly cisplatin-paclitaxel (CP) regimen with Cis. METHODS: Patients with LAHNSCC receiving definitive chemoradiation either with Cis (Cisplatin-100 mg/m2 q3w x 3) or CP (Cisplatin-20 mg/m2 ; Paclitaxel-30 mg/m2 qw x7) were included. RESULTS: Cis and CP groups were comprised of 114 and 111 subjects, respectively. Complete response for Cis versus CP groups was 88% versus 88%, respectively. Median follow-up for the study was 58.5 months. After adjusting for potential treatment selection bias, no significant differences were evident between Cis and CP groups for overall survival (hazard ratios [HR] 0.85, 95% CI 0.59-1.21, P = 0.36), progression free survival (HR 0.88, 95% CI 0.62-1.24, P = 0.46), locoregional control (HR 0.77, 95% CI 0.52-1.15, P = 0.21), and distant control (HR 0.87, 95% CI 0.61-1.23, P = 0.42). Patients in the CP group had less acute and chronic toxicities. CONCLUSIONS: Weekly CP regimen can serve as an alternative systemic therapy with radiation in patients with LAHNSCC who are not fit for Cis.

Is More Always Better? An Assessment of the Impact of Lymph Node Yield on Outcome for Clinically Localized Prostate Cancer with Low/Intermediate Risk Pathology (pT2-3a/pN0) Managed with Prostatectomy Alone.

The clinical impact of lymph node dissection extent remains undetermined in the contemporary setting, as reflected in care pattern variations. Despite some series demonstrating a direct relationship between number of lymph nodes identified and detection of nodal involvement, the correlation between lymph node yield and disease control or survival outcomes remains unclear. Patients with clinically localized prostate cancer, pre-RP PSA <30, and pT2-3a/N0 disease at RP were retrospectively identified from two databases for inclusion. Those who received pre- or post-RP radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences between subsets. From 2002 to 2010, 667 eligible patients were identified. The median age was 61 yrs. (range, 43-76), with median PSA 5.6 ng/dL (0.9-28.0). At RP, most patients had pT2c (64%) disease with Gleason Score (GS) ≤6 (43%) or 7 (48%); 218 (33%) patients had positive margins (M+). At median clinical and PSA follow-up of 96 and 87 months, respectively, 146 patients (22%) experienced PSA failure with an estimated bRFS of 81%/76% at 5/8 years. For patients who underwent LND, univariable analysis identified PSA (at diagnosis), higher GS (≥7, at biopsy or RP), intermediate/high risk stratification, M+ as adversely associated with bRFS (all p < 0.01). A higher number of LNs excised was not associated with improved bRFS for the entire cohort (HR = 0.97, p = 0.27), nor for any clinical risk stratum, biopsy GS, or RP GS subgroup. This study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with substratification by clinical risk stratum or GS.

Radioiodine Ablation following Thyroidectomy for Differentiated Thyroid Cancer: Literature Review of Utility, Dose, and Toxicity.

Management recommendations for differentiated thyroid cancer are evolving. Total thyroidectomy is the backbone of curative-intent therapy, with radioiodine ablation (RAI) of the thyroid remnant routinely performed, in order to facilitate serologic surveillance and reduce recurrence risk. Several single-institution series have identified patient subsets for whom recurrence risk is sufficiently low that RAI may not be indicated. Further, the appropriate dose of RAI specific to variable clinicopathologic presentations remains poorly defined. While recent randomized trials demonstrated equivalent thyroid remnant ablation rates between low- and high-dose RAI, long-term oncologic endpoints remain unreported. While RAI may be employed to facilitate surveillance following total thyroidectomy, cancer recurrence risk reduction is not demonstrated in favorable-risk patients with tumor size ≤1 cm without high-risk pathologic features. When RAI is indicated, in patients without macroscopic residual disease or metastasis, the evidence suggests that the rate of successful remnant ablation following total thyroidectomy is equivalent between doses of 30-50 mCi and doses ≥100 mCi, with fewer acute side effects; however, in the setting of subtotal thyroidectomy or when preablation diagnostic scan uptake is >2%, higher doses are associated with improved ablation rates. Historical series demonstrate conflicting findings of long-term cancer control rates between dose levels; long-term results from modern series have yet to be reported. For high-risk patients, including those with positive surgical margins, gross extrathyroidal extension, lymph node involvement, subtotal thyroidectomy, or >5% uptake, higher-dose RAI therapy appears to provide superior rates of ablation and cancer control.

Gleason Score ≤ 6 Prostate Cancer at Radical Prostatectomy: Does a High-Risk Setting Truly Exist? A Recursive Partitioning Analysis.

BACKGROUND: The purpose of this study was to determine whether a "high-risk" subpopulation of low-grade (Gleason score ≤6) prostate cancer defined by lower prostate-specific antigen (PSA) relapse-free survival (bRFS) might be identified within a large population of men who underwent radical prostatectomy (RP) alone, with mature follow-up. PATIENTS AND METHODS: Patients were retrospectively identified for inclusion by cT1-2 prostate cancer managed with RP alone. Exclusion criteria were: Gleason score ≥7 at RP, any pre- or post-RP radiotherapy or hormone therapy, or PSA follow-up <12 months. The Kaplan-Meier method was used for survival estimates; recursive partitioning by conditional inference analysis was applied to identify variables associated with bRFS. RESULTS: From 2002 through 2010, 284 eligible patients were identified. Median age was 60 years (range, 44-76 years), 233 (82%) were cT1c, and median PSA was 5.3 ng/dL (92% ≤10). The median biopsy to RP interval was 50 days (range, 11-410, with 97% <180 days). Eighty patients (28%) had positive margin (M+). At a median follow-up of 92.6 months (range, 16.9-160.9, with 45% followed ≥ 8 years), 32 patients (11%) had PSA failure, with an estimated 8-year bRFS rate of 89%. In univariate analysis, M+, extraprostatic extension, detectable initial post-RP PSA, and longer biopsy to RP interval were significantly associated with lower bRFS. M+ and longer biopsy to RP interval remained significant in multivariable analysis. Recursive partitioning analysis identified M+ as the only stratification factor, with 8-year bRFS estimates of 74% versus 95% for M+ versus margin-negative. CONCLUSION: Gleason score ≤6 prostate cancer managed using RP alone is associated with high rates of bRFS; however, margin positivity predicts early PSA failure rates in >20% of patients.

Once Daily High-dose Radiation (≥60 Gy) Treatment in Limited Stage Small Cell Lung Cancer.

BACKGROUND: To investigate outcomes and prognostic factors in patients treated with once daily high-dose (≥60 Gy) radiation therapy (HDRT) and concurrent platinum-based chemotherapy in limited stage small cell lung cancer (LS-SCLC). While we await current phase III trials to determine optimal radiation dose fractionation schemes in LS-SCLC, we report our experience in LS-SCLC with once daily HDRT. We hypothesized that HDRT would achieve similar efficacy and tolerability as twice daily therapy. METHODS: We conducted a single institution retrospective review of all patients with LS-SCLC who underwent curative intent treatment from 2005-2013. Patients treated with HDRT (≥60 Gy) and concurrent chemotherapy (cisplatin or carboplatin and etoposide) were included in our analysis. Clinicopathologic variables assessed include gender, performance status, time to treatment, response to treatment, toxicity, volumetric tumor response at 3 months, and use of prophylactic cranial irradiation (PCI). RESULTS: 42 patients with LS-SCLC who initiated concurrent chemoradiation from 2005 to 2013 were included in the analysis. 38 patients (90%) completed definitive treatment to the lung; 16 (38%) also completed PCI. Median failure free survival (FFS) and overall survival (OS) were 11.9 and 23.1 months, respectively. Two-year and 5-year OS rates were 47% (CI=30-62%) and 21% (CI=7-38%), respectively. On univariate analysis, PCI was associated with improved FFS but this was not significant (p=0.18). Gender was the only co-variate significantly associated with statistical differences in FFS (p=0.03) and OS (p=0.02). Grade 3 and 4 esophagitis were 10.5% and 2.6%, respectively. Pre-HDRT tumor volume and 3-month post-treatment tumor volume were both associated with FFS (p<0.01) but not OS. CONCLUSIONS: In this single institution series, daily HDRT demonstrated a 2-year OS of 47% in LS-SCLC. This compares well to the historical survival of daily fractionation (47%) from INT 0096 reported by Turrisi et. al. Male gender was predictive of significantly worse FFS and OS. Once daily HDRT has similar OS to twice-daily radiation schemes; however, further studies assessing once daily HDRT for LS-SCLC are warranted.

Incidental prostate cancer diagnosed at radical cystoprostatectomy for bladder cancer: disease-specific outcomes and survival.

BACKGROUND: The current standard of care for men with muscle-invasive bladder cancer is radical cystoprostatectomy (RCP). One-third of RCP specimens demonstrate incidental prostate cancer, primarily reported in small series with limited follow-up. The aim of this study is to report mature outcomes, including patterns of failure and disease-specific recurrence rates, and survival, for a large cohort of men with incidental prostate cancer at RCP performed at a tertiary referral center. METHODS: This retrospective study describes cancer control and survival rates for men who underwent RCP for bladder cancer and were found incidentally to have prostate cancer. Analysis of patient-, tumor-, and treatment-specific factors were analyzed for association with disease control and survival endpoints. RESULTS: Between 2002 and 2010, 94 patients with incidental discovery of prostate cancer postRCP were identified for inclusion in this study. Forty-five patients (45%) underwent RCP for recurrent (rather than initial presentation of) bladder carcinoma. At a median follow-up of 40.3 months (71.2 months for survivors; range, 8.9-155.5 months), 42 patients were alive without recurrence and 52 patients had died (25 associated with disease). The estimated 5-year bladder cancer disease-free, urinary tract malignancy disease-free, and prostate specific antigen (PSA) relapse-free survivals were 76% [95% confidence interval (CI), 65-84%], 64% (52-74%), and 97% (79-100%), respectively. The estimated 5-year urinary tract malignancy-specific and overall survivals were 61% (49-71%) and 52% (41-62%), respectively. Univariate analysis demonstrated associations between pathologic T/N-stage and nodal ratio with bladder cancer disease-free, urinary tract malignancy disease-specific, and overall survivals, with patient age at diagnosis as an additional adverse factor associated with overall survival. Multivariate analysis confirmed pN-stage and age as independently associated with worse survival. CONCLUSION: For men undergoing RCP for bladder cancer, the present study suggests that incidentally discovered prostate cancers, irrespective of pathologic stage, Gleason score, or clinical significance, do not impact 5-year disease control or survival outcomes.

Individualization of Adjuvant Therapy After Radical Prostatectomy for Clinically Localized Prostate Cancer: Current Status and Future Directions.

Radiation therapy indications in the postprostatectomy setting are evolving. Several retrospective series have identified a number of "high-risk" pathologic features associated with an elevated risk of disease recurrence after radical prostatectomy. More recently, several randomized phase III trials demonstrated superior biochemical relapse-free survival for adjuvant radiation therapy after prostatectomy for patients with these high-risk pathologic features, including positive margin status, extraprostatic extension, and/or seminal vesicle invasion. These series further suggested improvement in distant metastasis control and overall survival after 15 years. However, not all patients with high-risk features experience disease recurrence after surgery alone, and some subsets of patients experience suboptimal disease control and survival despite immediate postoperative radiotherapy. Furthermore, some patients without high-risk features will develop recurrence. The present review discusses the current data and potential future directions to improve individualization of therapy after prostatectomy.

Margin details matter: The prognostic significance of pseudocapsule invasion at the site of involved margin in prostatectomy specimens.

BACKGROUND: An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate pseudocapsule invasion vs. within the prostate parenchyma proper. METHODS: Patients were retrospectively identified for inclusion by clinically localized disease and prostate-specific antigen (PSA) level of< 30 ng/ml at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/nonsalvage postoperative radiation or hormone therapy, or insufficient follow-up (<12 mo). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of pseudocapsule invasion at a site of margin involvement. Disease recurrence was defined as PSA level of ≥ 0.2 ng/ml and rising, per contemporary guidelines. Kaplan-Meier method was used for construction of disease control estimate confidence intervals; Cox Proportional Hazards Model was used to compare disease control across groups. RESULTS: Between 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had clinical stage T1 and T2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8-9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA level of 5.6 ng/ml (85%≤ 10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the pseudocapsule. At a median follow-up of 68 months (range: 13-137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of pseudocapsule invasion vs. prostate parenchyma were 49% vs. 34%, respectively (P = 0.017; hazard ratio = 1.853). CONCLUSIONS: Early PSA relapse rates are high for patients with involved surgical margin(s) without seminal vesicle or node involvement at prostatectomy; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of pseudocapsule invasion or penetration confers a higher risk of recurrence.

Margin involvement at prostatectomy for clinically localized prostate cancer: does a low-risk group exist?

PURPOSE: To determine whether additional pathology details may provide risk stratification for patients with involved surgical margins at radical prostatectomy (RP). METHODS AND MATERIALS: Eligible patients underwent RP between 2003 and 2010. Patients with preoperative prostate-specific antigen (PSA) ≥20, follow-up <12 months, lymph node or seminal vesicle involvement, or who received radiation therapy or hormone therapy prior to PSA relapse were excluded. Surgical specimens were reviewed by a study pathologist, blinded to outcomes. Survival analysis methods were employed to assess disease control and survival rates, as well as association of patient-, tumor-, and treatment-specific factors for endpoints. RESULTS: Of 355 RP cases, 279 patients were eligible for the present analysis. At a median follow-up of 53 months (range, 16-127), 31/114 (27%) of patients with involved surgical margins experienced PSA relapse, as compared with 7/165 (4%) for negative margins (hazard ratio, 4.997; 95% confidence interval, 2.425-10.296; P < .0001). Detailed pathology review demonstrated associations between PSA relapse and Gleason score at RP, extent of margin involvement (width), capsule penetration, and perineural invasion. Subgroup analysis identified low risk (4%) of 5-year PSA relapse for patients with Gleason ≤6 mm and margin width ≤4 mm (single maximal or cumulative). All subgroups with higher Gleason score or wider margin were associated with >20% risk of PSA relapse at 5 years. CONCLUSIONS: Within the present study, Gleason score, 6 patients with margin width ≤4 mm appear to have low rates of early PSA relapse following RP. Low-grade cases with larger extent of margin involvement or higher risk Gleason score patients with any margin involvement have high rates of early PSA relapse.

What is the optimal management of Gleason score 7 prostate cancer at biopsy? A comparison of disease control for prostatectomy versus radiotherapy.

OBJECTIVES: To compare outcomes between radical prostatectomy (RP) or radiotherapy (RT) approaches for Gleason 7 (GS7) prostate cancer. METHODS: Patients were retrospectively identified for inclusion by clinically localized disease, GS7, prostate-specific antigen (PSA) < 30 ng/mL at diagnosis, and follow-up with PSA at > 12 months. Comparison of demographic, tumor, staging, and outcome variables was performed. Disease recurrence was defined as per contemporary society guidelines. The Kaplan-Meier method was used for disease control estimates. RESULTS: Between 2003 and 2010, a total of 253 patients were diagnosed with GS7 prostate cancer, of whom 207 were eligible for the current analysis (120 RP, 87 RT). Excepting older age for RT patients (median 73 vs. 62 years), the groups were well balanced. For RP patients, 82 patients (60%) had at least 1 high-risk feature, 4 (5%) of whom received adjuvant RT. For RT patients, 71 patients (82%) received hormone therapy (median duration 6 months). At a median follow-up of 62.2 months (range 13.1-136.6 months, with no difference between treatment groups), 64 patients had PSA relapse (51 RP, 13 RT), and 15 had died (5 of or with disease). PSA relapse-free survival was inferior for RP versus RT (P < .0001), with 5-year rates of 55.4% versus 82.6%, respectively. CONCLUSION: For GS7 prostate cancer patients, RT is associated with superior disease-free survival at 5 years compared to RP alone, without difference in disease-specific survival. Whether this difference remains in the setting of appropriately used adjuvant RT after RP, and the effect of possible delay in testosterone recovery for older RT patients remain to be determined.

An exploratory study of the relation of population density and agricultural activity to hematologic malignancies in North Dakota.

INTRODUCTION: Established risk factors for hematologic cancers include exposure to ionizing radiation, organic solvents, and genetic mutation; however, the potential roles of environmental and sociological factors are not well explored. As North Dakota engages in significant agricultural activity, the present investigation seeks to determine whether an association exists between the incidence of hematologic cancers and either population density or agricultural occupation for residents of south central North Dakota. METHODS: The present study is a retrospective analysis. Cases of hematologic malignancies and associated pre-malignant conditions were collected from the regional Central North Dakota Cancer Registry, and analysis of study-specific demographic factors was performed. RESULTS: Significantly higher incidence of hematologic cancers and pre-malignant disorders was associated with residence in an "urban" county and rural city/town. Within the latter designation, there was a higher rate of self-reported agricultural occupation (40% vs 10%, P < 0.0001). CONCLUSIONS: The increased incidence of hematologic cancer in low population density areas of south central North Dakota supports the need for more detailed prospective research centered on agricultural exposures.

Requirement of percutaneous endoscopic gastrostomy tube placement in head-and-neck cancer treated with definitive concurrent chemoradiation therapy: An analysis of clinical and anatomic factors.

PURPOSE: There is significant variation in recommendation for percutaneous endoscopic gastrostomy (PEG) tube placement in patients undergoing definitive chemoradiation therapy (CRT) for locally advanced squamous cell carcinoma of the head and neck (LAHNC), with some clinicians globally recommending prophylactic PEG and others waiting until toxicity has occurred. The present study was conceived to identify specific factors associated with PEG requirement, in a population of LAHNC patients who did not have up-front PEG placement. METHODS AND MATERIALS: Using a quality assurance database, we identified patients with oropharyngeal (ORP) or laryngeal-hypopharyngeal (LHP) LAHNC who were treated with CRT for inclusion in a cohort study of factors impacting PEG placement. Eligibility included stage III/IV squamous cell carcinoma of ORP and LHP. Patients were excluded if they had a PEG placement prior to commencement of CRT. The primary endpoint compared across groups was PEG placement, and multivariate analysis of factors was performed. RESULTS: We identified 107 patients with LAHNC who did not receive PEG tubes prior to treatment. After treatment initiation, 41% of patients with ORP tumors required PEG placement during treatment compared with 16% of LHP patients (P = .03). After adjusting for covariates, multivariate analysis revealed that the only predictor for PEG placement was ORP primary (odds ratio 4.77; 95% confidence interval 1.6-13.8, P = .009) using LHP as reference. CONCLUSIONS: Our findings suggest that the patients with ORP cancers are more likely to require PEG placement during treatment and should be considered for prophylactic PEG placement, while LHP sites were associated with lower likelihood of PEG requirement. The primary reason for this difference appears to be severity of pharyngitis; proactive nutritional monitoring and supplementation should be implemented early. Patients with pretreatment risk stratification for PEG placement in LAHNC may improve quality of care and avoid unnecessary treatment breaks.

Irradiation of donor mononuclear cells for treatment of chemorefractory metastatic solid cancers: a community-based immune transplant pilot study.

PURPOSE: Chemotherapy has demonstrated ability to generate tumor antigens secondary to induction of apoptosis, against which human leukocyte antigen-compatible, irradiated, related donor mononuclear cells may be administered with immune stimulation to activate antigen presenting and cytotoxic T cells, while minimizing risk of graft-versus-host disease (GVHD). The present study endeavours to describe feasibility and efficacy of this treatment, specifically in the community setting. MATERIALS AND METHODS: Eligible patients had rapidly progressive, chemorefractory metastatic solid tumors. Treatment consisted of intravenous etoposide and cyclosporine for three days followed by granulocyte-macrophage colony-stimulating factor for 5 days. The following week, 5×10(7) haploidentical or more closely matched irradiated donor mononuclear cells were given weekly for 10 weeks along with interleukin-2. RESULTS: Three patients were enrolled, and the regimen was well-tolerated, with no GVHD observed. All patients had clinical response, despite advanced and heavily pretreated disease. CONCLUSION: The above-outlined protocol demonstrates favorable tolerability and efficacy, and appears to be feasible in the community setting. While the optimal chemotherapy, immunostimulation, and irradiation regimens may be further optimized, future investigation appears warranted, and may include community oncology programs.

Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups.

PURPOSE: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups. METHODS: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) ≤ 3 cm, and ≤ 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF). RESULTS: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06). CONCLUSIONS: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.

Salvage Resection for Isolated Local and/or Regional Failure of Head/Neck Cancer Following Definitive Concurrent Chemoradiotherapy Case Series and Review of the Literature.

BACKGROUND: Primary management of advanced head/neck cancers involves concurrent chemoradiotherapy . Subsequently, regional and local failures are managed with resection but there have been few reports that describe the morbidity and disease control outcomes of surgical salvage in this setting. METHODS: Retrospective analysis describes complications, survival, and patterns of failure after salvage resection of isolated local and/or regional failures of head/neck cancer following definitive concurrent chemoradiotherapy. RESULTS: Sixteen patients were identified for inclusion: laryngectomy in 11 patients, oral cavity/oropharynx resection in 2 patients, and neck dissection alone in 4 patients. Ten patients required graft tissue reconstruction (6 pedicle and 4 free flap). Median post-operative hospitalization was 7 days (range 3-19), and 4 patients required hospital re-admission. At a median survivor follow-up of 15.8 months (range 4.3-34.9), 10 patients were alive (6 without evidence of disease). Seven patients experienced disease recurrence at a median 6.7 months (range 0-12.6) following salvage resection (2 with isolated distant failures). Estimated 2-year local/regional control, freedom from failure, and overall survival were 58%, 39%, and 58%, respectively. CONCLUSIONS: Surgical salvage after primary definitive concurrent chemoradiotherapy is feasible with toxicity and outcomes similar to prior radiotherapy alone or sequential chemotherapy and radiation. Local andregional recurrence remains the predominant pattern of failure.

Toxicity, response rates and survival outcomes of induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy for locally advanced esophageal cancer.

OBJECTIVE: Cisplatin-based chemoradiotherapy is standard treatment for locally advanced esophageal and gastroesophageal cancers; however, the optimal chemotherapy regimen remains to be defined. METHODS: Retrospective single institution analysis of toxicities, response rates and survival outcomes in patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated with induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy. Secondary analysis for association of disease control and outcomes with demographic, tumor and treatment factors (including histology). RESULTS: Fifty-three patients were eligible for the present analysis. All patients underwent endoscopic ultrasonography and were either cT3-4 and/or cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4 Gy, range 0-61.2), and 35 patients completed four cycles of chemotherapy as planned (range 1-4). Severe acute toxicities included Grade ≥ 3 neutropenia and esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal) toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7-63), 17 patients were alive (8 without disease) and 36 deceased. Forty patients experienced disease recurrence, with initial loco-regional, distant or both failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival and freedom from failure were 42 and 9%, respectively, without significant difference by histology. CONCLUSIONS: Cisplatin/irinotecan chemoradiotherapy is tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma esophageal cancers.

Involved-field radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer: disease control, patterns of failure and survival.

INTRODUCTION: Major randomised trials have employed elective nodal irradiation as part of combined modality therapy for limited-stage small-cell lung cancer (SCLC). The present investigation describes patterns of failure, disease control, and survival outcomes for involved-field radiotherapy with concurrent chemotherapy, without elective irradiation of uninvolved mediastinal nodal regions. METHODS: Retrospective analysis of SCLC patients treated with curative-intent accelerated, twice-daily radiotherapy and concurrent platinum-based chemotherapy at an academic institution. Treatment fields were reviewed, and patients who completed ≥42 Gy in 1.5 Gy twice-daily fractions to involved fields (without elective irradiation of uninvolved mediastinal lymphatic regions) were included in the present analysis. Initial patterns of failure, disease control and overall survival were recorded. RESULTS: Fifty-two patients fulfilled study criteria and were included in the present analysis. All but one patient completed three to four cycles of chemotherapy, and 10 patients experienced grade 3 acute esophagitis. At a median survivor follow-up of 35 months (range 5.5-91.9), 22 patients were alive (15 without recurrence) and 30 had died (23 of/with disease, four of unknown cause, two of other cause and one of treatment toxicity). Initial site(s) of disease failure were loco-regional only (11 patients), distant only (14) and loco-regional plus distant (3). There were no cases of isolated out-of-field mediastinal recurrence in the absence of supraclavicular or more distant disease. The estimated 3-year disease-free and overall survivals were 36% and 44%, respectively. CONCLUSIONS: Involved-field radiotherapy did not appear to have an adverse impact on the anticipated patterns of failure, disease control, or overall survival in this population of limited-stage SCLC patients.

Imaging applications in multicatheter brachytherapy for soft tissue sarcomas.

Multicatheter brachytherapy can be applied as a monotherapy or in combination with external beam radiotherapy as an adjuvant treatment for soft tissue sarcoma. Successful application of brachytherapy in the treatment of soft tissue sarcoma requires implementation of multiple imaging modalities during preoperative and postoperative planning. Preoperative imaging is essential in planning local therapy for soft tissue sarcoma in that it defines the proximity of the tumor to adjacent critical structures, predicts the likelihood of close or positive surgical margins, and aids in defining the target volume for a brachytherapy implant. In the postoperative setting, imaging is utilized to assess the accuracy of target volume coverage and integrity of the implant, as well as in three-dimensional treatment planning.