Actuarial Disease-free Survival Research Articles

Does dose matter? Editorial comments to Morris et al. Whole prostate D90 and V100: A dose–response analysis of 2000 consecutive 125I monotherapy cases

In this issue of Brachytherapy, Morris et al. ( [1] Morris W.J. Spadinger I. Keyes M. et al. Whole prostate D90 and V100: A dose-response analysis of 2000 consecutive 125-Iodine monotherapy cases. Brachytherapy. 2014; 13: 32-41 Abstract Full Text Full Text PDF Scopus (30) Google Scholar ) reviewed their experience with 2000 consecutive 125I prostate implants to determine which pretreatment- and treatment-related factors influenced prostate-specific antigen (PSA; Phoenix) control. In this group of low- and intermediate-risk patients with a median followup of 5 year, the 5-, 7-, and 10-year actuarial disease-free survival (DFS) estimates were 96.0%, 94.4%, and 93.0%, respectively. Based on their analyses, they concluded “that dose metrics are not equivalent to oncologic endpoints and must be calibrated against DFS for each physician and each institution offering low-dose-rate prostate brachytherapy.” The obvious question is “does dose matter?” Because there is ample evidence that higher radiation doses improve biochemical and local control after external beam radiation therapy, maybe the question should be narrowed to “does dose only matter for 125I prostate implants?” Rebuttal to Drs Stone and StockBrachytherapyVol. 13Issue 1Preview“… a man hears what he wants to hear and disregards the rest …”The Boxer, 1969, lyrics by Paul Simon Full-Text PDF Whole prostate D90 and V100: A dose–response analysis of 2000 consecutive 125I monotherapy patientsBrachytherapyVol. 13Issue 1PreviewTo examine the relationship between whole prostate dose metrics and disease-free survival (DFS) after 125I low-dose-rate prostate brachytherapy (LDR-PB). Full-Text PDF

Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: A single institutional experience

To report the outcome and toxicities of radical external beam radiotherapy (EBRT) and template-based high-dose-rate interstitial brachytherapy (ISBT) in patients diagnosed with cervical cancer undergoing inadvertent surgery, vault cancers, and vaginal cancers at our institution. Between January 2000 and December 2008, 113 patients (37patients of cervical cancer post-inadvertent surgery, 57 patients with vault cancers, and 19 patients with primary vaginal cancers) were treated with Martinez Universal Perineal Interstitial Template brachytherapy boost after EBRT. The median EBRT dose was 50Gy, median ISBT dose was 20Gy, whereas median total dose was 73Gy equivalent dose at 2Gy per fraction in all three groups. Median followup of surviving patients for the whole group was 43 months (interquartile range, 19-67 months). The 3-year actuarial disease-free survival and overall survival for three groups was 61%, 61%, 59% and 64%, 64%, and 56%, respectively. Grade III/IV rectal toxicity was seen in 11 (10%) patients, bladder toxicity in 5 (4.5%) patients, whereas 7 (6%) patients developed Grade III small bowel toxicity. Residual disease at brachytherapy had significant impact on DFS and OS. Other factors such as age, disease volume, parametrial extension, and vaginal extension did not impact the survivals. Martinez Universal Perineal Interstitial Template-based high-dose-rate ISBT boost in gynecologic cancer results in a reasonable outcome in terms of survivals with acceptable late toxicities. The use of template-based ISBT is associated with a definite learning curve.

Whole prostate D90 and V100: A dose–response analysis of 2000 consecutive 125I monotherapy patients

To examine the relationship between whole prostate dose metrics and disease-free survival (DFS) after (125)I low-dose-rate prostate brachytherapy (LDR-PB). Data for the first 2000 LDR-PB monotherapy implants were extracted from a database containing patient, tumor, dosimetric, and outcomes information. By National Comprehensive Cancer Network criteria, half (n = 1006) had low-risk disease and half (n = 990) had intermediate-risk disease (four had high-risk disease). Most patients (58.4%) and 75.3% of intermediate-risk patients received 3 months neoadjuvant and 3 months concomitant androgen deprivation therapy (ADT). Univariate and multivariate analyses were conducted using recognized prognostic factors and the whole prostate dose metrics D90 (the minimum dose received by 90% of the postimplant CT-based prostate volume) and V100 (the percent of the postimplant CT-based prostate volume that received at least 100% of the prescription dose). The median followup is 5 years (maximum, 12.5 years); the 5-, 7-, and 10-year actuarial DFS estimates are 96.0%, 94.4%, and 93.0%, respectively. Of the recognized prognostic factors, only pretreatment prostate-specific antigen (p = 0.012) and Gleason sum (p = 0.010) were predictive of DFS. When analyzed as continuous variables, dose metrics were not predictive of DFS. However, most nonsignificant trends favored higher doses, and D90 values <130 Gy were predictive of an increased risk of recurrence in the non-ADT subset (N = 833; log rank, p = 0.018). Although D90 values of <130 Gy were predictive of an increased risk of recurrence in the non-ADT subset, neither D90 nor V100, when used as continuous variables, was predictive of DFS when applied to the entire cohort or in the subset analysis. This observation informs us that dose metrics are not equivalent to oncologic end points and must be calibrated against DFS for each physician and each institution offering LDR-PB.

Dysplasia at the margin? Investigating the case for subsequent therapy in ‘Low-Risk’ squamous cell carcinoma of the oral tongue

This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue. Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed. 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52 months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p=0.005 and 49% vs 80%, p=0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p=0.02) and the effect of severe dysplasia at the margin was approaching significance (p=0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p=0.006) and DFS (HR: 2.84, p=0.008) associated with severe or moderate dysplasia at the margin. Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity.

DNA Ploidy Measured on Archived Pretreatment Biopsy Material May Correlate With Prostate-Specific Antigen Recurrence After Prostate Brachytherapy

To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival. Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate (125)I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used for the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities. The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with "excellent" dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as "nonexcellent" (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and "excellent" dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients. Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis.

Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Between 2001 and 2008, 65consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Median OS times were 18and 43months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14and 35months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade3 or secondary tumors were observed. After a median follow-up period of over 5years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

Recurrence after operative management of intrahepatic cholangiocarcinoma

Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC. We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥ 5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.

Phase I trial of total androgen blockade, weekly docetaxel, and image-guided intensity-modulated radiotherapy for localized high-risk prostate adenocarcinoma.

96 Background: High-risk prostate cancer patients have high rates of treatment failure and improved outcomes are needed. Docetaxel has shown efficacy in hormone-resistant prostate cancer and can act as a radiosensitizer. Dose escalation studies with radiation therapy have found improved freedom from failure rates. The addition of androgen deprivation therapy (ADT) improves overall survival. Therefore, this phase I study was designed to find the maximum tolerable dose (MTD) of weekly docetaxel when combined with high-dose image-guided intensity-modulated radiotherapy (IGRT) and ADT in patients with high-risk prostate cancer. Methods: Men with high-risk adenocarcinoma of the prostate (≥T2c, or PSA ≥20ng/ml, or Gleason ≥8) were treated with weekly docetaxel (given at 10-30 mg/m2, increasing by 5 mg/m2until the MTD was reached) concurrently with IGRT of 77.4 Gy in 43 fractions to the prostate and 45 Gy in 25 fractions to the proximal seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before chemoradiation and continuing 2 months concurrently. The GnRHa was then continued for an additional 24 months. Results: 19 patients began combined chemoradiation between April 2006 and December 2010. Median follow-up is 32 months. No dose-limiting toxicities (DLTs) were seen in patients treated with docetaxel doses up to 25 mg/m2. However, at the 30 mg/m2level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and grade 3 upper GI toxicity, indicating the MTD had been exceeded. At last follow-up, 2 patients had died, one from metastatic prostate cancer and the other from heart failure. A second patient demonstrated biochemical failure by the Phoenix criteria at 46 months, giving an actuarial biochemical disease-free survival (bDFS) at 3 years of 94.7%. All patients had ≥grade 2 erectile dysfunction but no other ≥grade 2 long-term toxicities were identified. Conclusions: Weekly docetaxel may be combined with high-dose IGRT and long-term ADT up to a MTD of 25 mg/m2. Long-term side effects with this regimen were minimal, and bDFS rate is encouraging. Clinical trial information: NCT00099086.

Population‐based 10‐year oncologic outcomes after low‐dose‐rate brachytherapy for low‐risk and intermediate‐risk prostate cancer

The objective of this study was to report the rates of disease-free survival (DFS), cause-specific survival (CSS), and overall survival after low-dose-rate (LDR) prostate brachytherapy (PB). Data from 1006 consecutive patients with prostate cancer who received LDR-PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low-risk (58%) or intermediate-risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty-five percent of patients received 3 months of neoadjuvant androgen-deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables. The median follow-up was 7.5 years. By using Fine and Gray competing risks analysis, the 5-year and 10-year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%-97.7%) and 94.1% (95% confidence interval, 92%-95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10-year CSS rate was 99.1% (95% confidence interval, 97.3%-99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%-95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%-86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis. In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low-risk and intermediate-risk prostate cancer, the actuarial rate of recurrent disease after LDR-PB was approximately 3% at 5 years and 6% at 10 years.

Abstract P4-15-01: Second conservative treatment for ipsilateral breast tumor recurrence: GEC-ESTRO Breast WG study

Abstract For ipsilateral breast cancer tumor (IBTR), radical mastectomy represents the treatment option frequently proposed to the patient. A second conservative treatment (SCT) has been proposed using either lumpectomy alone or associated with a second irradiation of the tumor bed. However, in both clinical situations, the proof level of such therapeutic approaches remains low, based on cased-series or retrospective studies. To analyze the clinical outcome of a SCT using lumpectomy and multicatheter interstitial brachytherapy (MIB) for IBTR, the GEC-ESTRO Breast Working Group retrospectively analyzed the results of 217 patients (pts) with an IBTR treated between 09/00 and 09/10 in 8 European institutions by lumpectomy and MIB (low - LDR, pulse - PDR, or high-dose rate - HDR). Survival rates without 2nd local (2nd LR) and metastatic recurrence, disease free survival (DFS) and specific and overall survivals were analyzed as well as late effects and cosmetic results. Dosimetric data were reported according to the dose rate used. Univariate and multivariate analysis were performed to find local, metastatic and/or DFS progression prognostic factors. With a median follow-up of 14.5 years [3.5–38.2] and 3.9 years [1.1–10.3] from primary tumor and IBTR respectively and a median time interval of 9.4 years [1.1–35.4] between primary and IBTR, 20.7% of the local recurrence were observed at distance from the primary tumor. Median tumor sizes were 15 mm [1–60] and 11 mm [1–40] for the primary and IBTR respectively. Thirty-nine percent of the patient underwent an axillary lymph node dissection at the time of IBTR. Median radiotherapy dose for the primary was 56 Gy [30–69.6]. Positive hormonal receptor status for IBCR was 72.8% while 65% and 19.8% received hormonal and chemotherapy respectively as adjuvant therapy for the IBTR. Five and 10-year actuarial 2nd LR rates were 5.6% [1.5–9.5] and 7.2% [2.1–12.1] respectively. Five and 10-year actuarial metastatic recurrence rates were 9.6% [5.7–15.2] and 19.1% [7.8–28.3] respectively. Five and 10-year actuarial DFS rates were 84.6% [78.9–90.6] and 77.2% [67.5–88.3] respectively. Five and 10-year actuarial overall/specific survival (OS) rates were 88.7% [83.1–94.8] and 76.4% [66.9–87.3] respectively. 141 pts developed 193 complications. Fibrosis was the most frequent complication with 11% of G3-4 complications. Cosmetic result was jugged as excellent/good in 85%. Focusing on multivariate analysis, prognostic factors for 2nd LR, metastatic recurrence and DFS are reported. The results of this study suggest that in case of IBTR, a SCT combining lumpectomy plus MIB is feasible with an overall survival rate at least equivalent to those obtain after salvage mastectomy. The rate of complication remains acceptable with encouraging cosmetic results. The literature analysis suggests that the rate of 2nd LR is 10% [3–32], 25% [7–36] and 10% [2–26], after salvage mastectomy, salvage lumpectomy alone or combined with a second irradiation respectively. However, the 5-y OS rates after salvage mastectomy and SCT seem to be equivalent (75%) mainly influenced by distant metastatic progression. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-01.

Complete metabolic response after definitive radiation therapy for cervical cancer: Patterns and factors predicting for recurrence

PurposeThe purpose of this study was to determine the patterns of failure in patients diagnosed with cervical cancer treated with definitive radiotherapy and who subsequently had complete metabolic response (CMR) seen on early post-therapy (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Additionally, we sought to determine what factors predict disease recurrence in this patient population. Methods and materialsWe reviewed the records of 155 patients diagnosed with cervical cancer from stages IB1 to IVA who were treated with definitive chemoradiation therapy between 2003 and 2011 and had a FDG-PET at 10–16weeks following completion of therapy. One hundred and twelve (72.0%) had CMR on follow-up FDG-PET and comprised the patients in this study. ResultsThe median age of patients with CMR was 51years and the median tumor size 4.9cm. Median follow up was 15months. Of the 112 patients, 11 (9.8%) had a recurrence and six (5.4%) had isolated local recurrences, and five (4.5%) had distant recurrence. Median time to recurrence was 9months. Three-year actuarial disease-free survival and overall survival rates were 78.9% and 88.0% respectively. On Cox regression multivariate analysis, tumor size was predictive of increased risk of local recurrence in these patients with CMR with p<0.025. Age, stage, histology and nodal positivity were not significant for predicting local, distant or any recurrence. ConclusionPatients treated with concurrent chemoradiation had a CMR which demonstrated good clinical outcomes in terms of local control. There were equal numbers of patients suffering local and distant recurrences. In patients with a CMR, only tumor size was an independent predictor for local recurrence.

Squamous cell carcinoma of buccal mucosa: a 40-year review

PurposeThe aim of this study was to analyze the outcome of surgical therapy for buccal squamous cell carcinoma (SCCA) at a single tertiary care institution during a 40-year period. Materials and methodsA retrospective review was performed by examining the records and pathology of 48 patients with buccal SCCA treated at a single tertiary care institution from 1970 to 2009. ResultsTreatment entailed surgery alone in 18 patients (37.5%) and surgery followed by radiation therapy in 30 patients (62.5%). Composite resection was performed in 17 patients (35.4%), and ipsilateral neck dissections were performed in 37patients (77.1%). One-year observed actuarial disease-free survival rates were 60%, 46%, 0%, and 40% for T1 through T4, respectively. Univariate analysis revealed increased age as a risk factor for disease recurrence (P = .062), with skin taken and neck dissection not achieving significance (P = .24 and .20, respectively). Multivariate analysis demonstrated age as increasing risk and neck dissection as decreasing risk of recurrence (P = .029 and .023, respectively). ConclusionsWe report relatively high disease-free survival rates in patients who underwent aggressive resection and neck dissection. Performance of neck dissection and younger age were associated with a favorable prognosis. Performance of neck dissection may decrease the risk of recurrence in primary SCCA of the buccal mucosa. Although through-and-through resection of skin decreased risk of disease recurrence, this difference is not statistically significant (P = .24).

Postoperative periclavicular radiotherapy in breast cancer patients with 1–3 positive axillary lymph nodes

The goal of this work was to examine the possible influence of periclavicular irradiation on outcome of breast cancer patients with 1-3 positive lymph nodes with special emphasis on late toxicity rates. Between 1997 and 2000, 235breast cancer patients (T1-2, 1-3 involved lymph nodes) were treated at our department following breast conservative surgery: 139patients (59.1%) had one, 62patients (26.4%) two, and 34patients (14.5%) three positive lymph nodes. Extracapsular spread (ECS) was described in 72patients (30.6%). There were 67patients (28.5%) who received additional radiotherapy to the ipsilateral periclavicular lymph nodes (PCLNI), while 168patients did not (noPCLNI). Patients were re-examined or contacted by phone with regard to treatment-related late effects. After a median follow-up of 78months (range 7-107months), 22patients (9.4%) developed local, 9(3.8%) axillary, 4periclavicular (1.7%), and 41distant failure (17.4%). The actuarial 8-year locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs. noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70% (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI group compared to the noPCLNI group. We could not demonstrate any difference in outcome in breast cancer patients with 1-3 positive axillary lymph node metastases with or without periclavicular lymph node irradiation. In addition, patients with PCLNI did not complain about higher rates of late toxicities. However, patients with ECS, which may predict for locoregional failure, may benefit from adjuvant periclavicular irradiation.

Preoperative taxane‐based chemotherapy in a standardized protocol for locally advanced breast cancer

To assess the feasibility of a standardized multidisciplinary protocol for the management of locally advanced breast cancer (LABC). We also evaluated the accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) in predicting the extent of residual disease. Patients with LABC were offered preoperative chemotherapy of docetaxel 75 mg/m(2) , doxorubicin 50 mg/m(2) , cyclophosphamide 500 mg/m(2) (TAC), every 21 days for six cycles, until progression or intolerable toxicity. MRI and PET were performed at baseline and six cycles. Patients underwent a mastectomy or complete local excision, followed by radiotherapy. Trastuzumab and endocrine treatment were recommended where appropriate. Between April 2005 and October 2006, 51 patients were included from three institutions, and 50 received TAC (90% commenced within 35 days of diagnosis), with 44 patients completing six cycles (88%). Pathological complete response was seen in 10 patients (19.6%); all had invasive ductal carcinoma. No patient with invasive lobular carcinoma achieved pathological complete response. MRI was the most accurate method of assessing the extent of residual cancer. In total, 45 (88%) patients underwent surgery within the protocol-specified time and 12 (23%) patients had breast conservation surgery. At a median follow-up of 41.3 months, there were three local recurrences. Ten patients (19.6%) developed distant metastases, resulting in an 80% actuarial disease-free survival. This regimen of TAC is effective and well-tolerated and is likely to result in improved outcomes since patients can receive optimal multimodality treatments.

Prevention of Peritoneal Metastases from Colon Cancer in High-Risk Patients: Preliminary Results of Surgery plus Prophylactic HIPEC

The study compared the outcome in patients with advanced colonic cancer at high risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal or systemic spread, treated with standard colectomy or a more aggressive combined surgical approach. The study included patients with colonic cancer with clinical T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in the experimental group underwent hemicolectomy, omentectomy, bilateral adnexectomy, hepatic round ligament resection, and appendectomy, followed by HIPEC. The control group comprised 50 patients treated with standard surgical resection during the same period in the same hospital by different surgical teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and disease-free survival, were compared. Peritoneal recurrence developed in 4% of patients in the experimental group and 22% of controls without increasing morbidity (P < 0.05). Actuarial overall survival curves disclosed no significant differences, whereas actuarial disease-free survival curves showed a significant difference between groups (36.8 versus 21.9 months, P < 0.01). A more aggressive preventive surgical approach combined with HIPEC reduces the incidence of peritoneal recurrence in patients with advanced mucinous colonic cancer and also significantly increases disease-free survival compared with a homogeneous control group treated with a standard surgical approach without increasing morbidity.

Total pelvic exenteration for rectal cancer: outcomes and prognostic factors

To perform complete resection of locally advanced and recurrent rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified disease-related outcomes and prognostic factors. We conducted a single-centre review of patients who underwent TPE for rectal carcinoma over a 10-year period. We included 28 patients in our study. After a median follow-up of 35 months, 53.6% of patients were alive with no evidence of disease. The 3-year actuarial disease-free and overall survival rates were 52.2% and 75.1%, respectively. On univariate analysis, recurrent disease, preoperative body mass index greater than 30 and lymphatic invasion were poor prognostic factors for disease-free survival, and only lymphatic invasion predicted overall survival. Additionally, multivariate analysis identified lymphatic invasion as an independent poor prognostic factor for disease-free survival in this patient population with locally advanced and recurrent rectal carcinoma. Despite the significant morbidity, TPE can provide long-term survival in patients with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an independent prognostic factor for disease-free survival.

Primary tumor size, not race, determines outcomes in women with hormone-responsive breast cancer

We sought to determine if there was a difference in outcomes in African-American compared with Caucasian women with hormone-responsive breast cancer, and whether this was related to race or other tumor and treatment variables. We included 1,205 patients with hormone-responsive breast cancer were identified in the Kentucky Cancer Registry (1996-2007). The effect of race on survival was evaluated using Kaplan-Meier and Cox regression methodologies. In this cohort, 76.9% were Caucasian and 21.7% were African American. Compared with Caucasians, African-American women were older (57 vs 55 years; P = .032) and more likely to have larger tumors (19 vs 17 mm; P = .009). No significant racial differences in grade, operative, or systemic treatment were noted. Univariate analysis found no significant differences in disease-specific overall survival (DSS) or disease-free survival (DFS) between Caucasians and African Americans (5-year actuarial DSS, 93.6% vs 90.7%, respectively; P = .205; 5-year actuarial DFS, 91.5% vs 90.4%, respectively; P = .829). On multivariate analysis, only tumor size remained an independent predictor of DSS (odds ratio [OR], 1.021; 95% confidence interval [CI], 1.013-1.028; P < .001). Controlling for age, tumor size, and insurance status, race did not influence DSS or DFS (P = .913 and P = .857). African Americans present with larger tumors than Caucasians; treatment is similar. Tumor size, not race, affects disease-specific outcomes in patients with breast cancer.

Efficacy analysis of high-risk breast cancer patients treated with accelerated partial breast irradiation from a single institution.

111 Background: We present the results of an analysis of high-risk breast cancer patients as defined by the NSABP B-39/RTOG 0413 phase III trial, all treated with accelerated partial breast irradiation (APBI) from a single institution. Methods: Between July 1993 and August 2010, 130 patients with any combination of at least one of the high-risk features of estrogen receptor (ER) negativity, age &lt; 50, and/or axillary nodal positivity were treated with 1 of 3 forms of APBI. Sixty-seven patients were treated with interstitial needle-catheter brachytherapy, 44 balloon-based brachytherapy and 19 with 3D conformal external beam radiation therapy. Aside from the high-risk features, general eligibility criteria included infiltrating ductal carcinoma, with inclusion of invasive lobular and DCIS since 2003, margins &gt; 2 mm, and surgically staged axilla. One-hundred eighteen patients had one high-risk factor, 11 had two, and 1 had all three factors. The median tumor size was 12.0 mm with margins &gt; 2 mm in 80% of patients. Greater than 75% had T1 tumors and 50% were ER negative. Thirty-one percent of patients were node positive. Based upon the ASTRO Consensus Guidelines for use of APBI (2009) none of these patients were suitable, 38% cautionary and 62% were unsuitable. Results: Median age was 56.5 yrs (range 40-90). With a median follow-up of 5.3 yrs (0.02-16.9) the 5-yr actuarial local recurrence rate (LR) was 4.2%; regional recurrence (RR) was 2.1%. Median time to LR and RR were 1.2 and 2.8 yrs, respectively. On univariate analysis, the only factor significant for LR was a close/positive margin (p=0.031), as ER/PR, age, nodal status, tumor size, histology, grade, hormonal or chemotherapy were all NS. The 5-yr actuarial cause specific, disease-free, and overall survivals as well as distant metastasis were 94%, 91%, 90%, and 6.4%, respectively. Conclusions: This cohort of NSABP B-39/RTOG 0413 identified high-risk patients who have undergone APBI has yielded local-regional control rates and survival outcomes comparable to standard risk patients undergoing partial breast irradiation. Continued follow-up will be needed to assess the long-term efficacy of such high-risk breast cancer patients treated with APBI.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: Results of a phase II study

Background. An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. Material and methods: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. Results: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12–55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18–63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1–2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. Conclusion. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Squamous Cell Carcinoma of the Buccal Mucosa: A 40‐Year Review

Objective: Evaluate the treatment results of buccal squamous cell carcinoma at a single institution during a 40-year period. Method: A retrospective review was performed by examining the records and reviewing the pathology of 48 patients with buccal squamous cell carcinoma treated at UCLA Medical Center from 1970 to 2009. Forty-eight patients were identified that received first-time surgical therapy for squamous cell carcinoma of the buccal mucosa and had adequate follow-up. Results: Treatment entailed surgery alone in 18 out of 48 patients (37.5%) and surgery followed by radiation therapy in 30 out of 48 patients (62.5%). Composite resection of the tumor was performed in 17 out of 48 patients (35.4%) and ipsilateral neck dissections were performed in 37 out of 48 patients (77.1%). One-year observed actuarial disease-free survival rates were 60%, 46%, 0%, and 40% for T1 through T4, respectively. Univariate analysis revealed increased age as a risk factor ( P = .062), and multivariate analysis demonstrated age as a risk factor and performance of neck dissection having a decreased risk of recurrence ( P = .029 and .023, respectively). Conclusion: We report fairly high disease-free survival rates in this patient population. Performance of neck dissection and younger age were associated with a favorable prognosis. Performance of neck dissection may decrease the risk of recurrences in primary squamous cell carcinoma of the buccal mucosa.