Significant Predictor Of Local Recurrence Research Articles

Impact of pathologic features on local recurrence in penile squamous cell carcinoma after penectomy

BackgroundPenile squamous cell carcinoma (PSCC) is a rare malignancy that may be cured in cases of local disease by resection of the primary tumor. Risk factors and patterns of local recurrence (LR) have not been well described in cases requiring partial or radical penectomy. In this study, we evaluated risk factors for LR and the impact of frozen and final margin assessment. Materials and methodsWe evaluated 119 patients with PSCC who had undergone partial or radical penectomy from 2007 to 2023. Data regarding clinical and pathologic features were collected by retrospective chart review. The primary outcome of interest was LR. Determinants of LR were analyzed by Student's t, Fisher's exact, chi-square and logistic regression analysis. Predictive statistics of frozen margin status on final margin were assessed and LR rates for subsets of frozen and final margin interaction were defined. Finally, all cases of positive margins and LR were described to highlight patterns of LR and the importance of margin status in these cases. ResultsThere were 8 (6.7%) cases of local recurrence. There were no significant predictors of LR, although a trend toward increased LR risk was observed among those with a positive final margin. Positive final margins were found in 15 (13%) cases. Frozen margin analysis was utilized in 79 cases, of which 10 (13%) were positive. The sensitivity, specificity, positive predictive value, and negative predictive value of frozen margin status for final margins were 44%, 92%, 40%, and 93%, respectively. There were no LR among cases in which frozen margin was not sent. Analysis of all cases with positive margin and/or LR identified three subsets of patients: CIS or focally positive margin resulting in either no LR or LR managed with minimal local intervention, bulky disease in which survival is determined by response to subsequent therapy rather than local recurrence, and clinically significant local recurrence requiring continued surveillance and intervention despite negative margins. ConclusionsLR is rare, even in cases of larger, proximal tumors requiring partial or radical penectomy. In this study, no statistically significant risk factors for local recurrence were identified; however, analysis of frozen and final margins provided insight into the importance of margin status and patterns of local recurrence. When feasible, visibly intra-operative negative margins are an excellent predictor of low risk for LR, and, in cases of CIS or focally positive margins, further resection to achieve negative margins is unlikely to reduce the risk of clinically significant LR. Additionally, in cases of bulky disease, the goals of resection should be focused toward palliation and next line therapy.

Transoral robotic surgery and neck dissection alone for head and neck squamous cell carcinoma: Influence of resection margins on oncological outcomes

ObjectivesThis study reports oncological outcomes of transoral robotic surgery (TORS) and neck dissection (ND) alone for head and neck squamous cell carcinoma (HNSCC) and aims to analyse the influence of resection margins on local recurrence rates. Materials and methodsFifty-one patients treated with curative intent for HNSCC, with TORS and ND alone between 2013 and 2019 at two tertiary centres were included in this observational multi-centre prospective cohort study. Oncological outcomes are reported on 47 patients for whom the aim was to treat with TORS and ND alone; this excluded four patients who were recommended adjuvant radiotherapy based on resective pathology but did not receive treatment. Local control is the primary endpoint; disease specific, progression free and overall survival are secondary outcomes. ResultsWith a median follow up of 43 months, estimated outcomes at 3 years (n = 47) were as follows: local control 92%, progression free survival 80%, disease specific survival 94%, and overall survival 84%. Presence of a positive margin on the main specimen was the only statistically significant predictor of local recurrence on univariate Cox regression analysis. Time dependent receiver operating characteristic curve identified margins of 1.1 mm as a threshold for local control, with area under the curve 0.788 (95% CI 0.616–0.960), indicating a good classifier. ConclusionThis is the first UK surgery alone series reporting mature oncological outcomes following TORS and ND. Positive margins on the resected specimen are the strongest predictor of local recurrence, with conventional definitions of “close margins” having no impact.

Predictive Value of Preoperative Magnetic Resonance Imaging Findings for Survival and Local Recurrence in Patients Undergoing En Bloc Resection of Sacral Chordomas.

Few studies have assessed the prognostic importance of preoperative magnetic resonance imaging (MRI) scan findings in patients undergoing en bloc resection of sacral chordomas. To (1) report in-depth imaging characteristics of sacral chordomas, (2) describe the patterns of local and distant recurrence, and (3) determine imaging predictors of overall survival (OS) and local recurrence (LR). This retrospective case series was obtained from a prospectively maintained spine database from 1995 to 2016. All patients underwent en bloc resection of sacral chordomas. Detailed demographic, outcome, and MRI data were collected. A survival analysis was completed with multivariable cox regression to assess the impact of MRI findings on OS and LR. A total of 41 patients underwent en bloc resection of sacral chordoma with preoperative MRI scans. Tumor characteristics included lobulated: (93%) and soft tissue tail (54%). The following areas had tumor invasion lobulated: sacroiliac (SI) joint (15%), ilium (5%), piriformis (61%), gluteus (46%), subcutaneous fat (32%), and lumbosacral venous plexus (22%). After multivariable analysis, only subcutaneous fat extension was an independent predictor of decreased OS (hazard ratio 5.30, 95% confidence interval 1.47-19.19, P=.011). Though not significant after multivariable analysis, the following factors were significant predictors of LR after univariate logrank testing: above the L5/S1 disc space (P=.004), SI joint invasion (P=.036), and piriformis extension (P=.022). The presence of subcutaneous fat extension was an independent predictor of decreased OS. Other MRI findings with potential for future evaluation include size, presence of soft tissue tail, extension above L5/S1, and SI joint and piriformis invasion.

An assessment of histological margins and recurrence of completely excised cutaneous SCC

There is a paucity of data relating to histological margins of cutaneous squamous cell carcinoma (cSCC) and local recurrence. Retrospective data were collected for 721 patients with cSCC treated at Queen Victoria Hospital, UK, and followed up for five years. The local recurrence rate was 6.1%, the mean time to recurrence was 12.61 months and 93% of recurrences occurred within two years. Sixty-six per cent of recurrences had a deep margin of 2.5 mm or less (p 0.041). The Pearson's correlation coefficient showed a strong correlation with tumour grade (r=0.82, p, 0.05), lymphovascular invasion (r=0.73. p<0.05), medium correlation with deep histological margin(r= -0.55, p<0.05), a weak correlation with male sex (r= 0.31, p<0.05) and the anatomical site of head and neck (r=0.31, p<0.05).The multiple regression analysis model using the 5 variables generated an r value of 0.71 and adjusted r square of 0.7. In conclusion, our findings are consistent with previously mentioned prognostic indicators and also demonstrate that deep histological margin is a significant predictor of local recurrence of cSCC. We recommend larger multi-institutional studies to confirm the above results to subsequently guide the specialist skin multidisciplinary teams' recommendations.

Factors affecting differential outcomes in the definitive treatment of anal cancer between HIV+ and HIV- patients.

3572 Background: Anal cancer is an uncommon malignancy with numerous factors that influence treatment outcomes. Historically, HIV+ patients were restricted from entering clinical trials, limiting data on their outcomes to small retrospective reports. This study seeks to understand the factors related to anal cancer outcomes, specifically the differences between HIV+ and HIV- patients. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Clinical data related to baseline characteristics, treatment parameters, and post-treatment follow-up were extracted for calculation of freedom from local recurrence (FFLR) and overall survival (OS). Univariate analysis (UVA) and multivariate analysis (MVA) were done using cox proportional hazard model, and FFLR and OS were calculated using the Kaplan-Meier method. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. Median age was 56.7 years (IQR: 51.4-63.5), and 47% (N = 52) were HIV+. At median follow-up of 28 months, 12 and 24-month FFLR was 84.1% and 78.2% respectively, with 24-month OS of 87.3%. MVA demonstrated significant association between FFLR and T-stage HR 4.02 (95% CI: 2.14-7.55) p &lt; 0.001, elapsed treatment time (median of 50 days) 1.08 (95% CI: 1.04-1.12) p &lt; 0.001, and diagnosis to treatment start (median time of 15 weeks) 1.05 (95% CI: 1.01-1.08) p = 0.005. Additional analysis with log-rank test for FFLR demonstrated significant difference between patients taking &lt; 50 days to complete treatment (p = 0.03), and &lt; 15 weeks from diagnosis to treatment completion (p = 0.006). In HIV+ patients, post-treatment CD4 &lt; 150 was significantly associated with worse OS on log-rank test (p = 0.016), with pretreatment CD4 values being non-significant. Conclusions: This study represents the largest single institution report of HIV positive patients treated for anal cancer. No difference in local recurrence or overall survival between HIV+ and HIV- patients was elucidated; however, HIV+ patients with lower post-treatment CD4 counts had worse OS. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time.

Lymphatic invasion is a cause of local recurrence after wedge resection of primary lung cancer.

After securing a sufficient surgical margin at wedge resection and finding no pathologic evidence of residual tumor at the surgical margin, a considerable number of patients develop local recurrence. We investigated the correlation between sub-pleural lymphatic flow and local recurrence. We retrospectively reviewed the medical records of 144 non-small cell lung cancer patients who underwent wedge resection between January 2006 and December 2014at our institution. Postoperative recurrence was observed in 36 patients (25%). Of these, local recurrence was observed in 29 patients (80.5%). The proportion of all recurrence and local recurrence were significantly higher among patients with lymphatic vessel invasion (LVI) (p < 0.0001). Recurrence-free survival rate was significantly lower in patients with LVI (24.8%) than in patients without LVI (80.2%, p < 0.0001). Multivariate logistic regression analysis demonstrated LVI (odds ratio = 6.420, p = 0.0009) as a significant predictor of local recurrence. Intratumoral lymphatic invasion represents a major cause of local recurrence. Although we should aim for radical surgery whenever possible, when limited surgery is the only option, postoperative adjuvant treatment may need to be considered for patients showing lymphatic invasion even at an early stage.

Impact of clinical and pathological factors on local recurrence after breast-conserving treatment: CT-based localization for a tumor bed boost yielded better local control when compared with a surgical scar.

Background: We investigated the effects of risk factors on the incidence of local recurrence (LR) in patients who underwent breast-conserving treatment (BCT) for primary breast cancer at a single institution in China from 1999 to 2011.Methods: Patient outcomes were compared with respect to LR, ipsilateral breast tumor recurrence (IBTR), distant disease-free survival (DDFS), and disease-free survival (DFS). Additionally, the risk factors for relapse after BCT were studied.Results: The 2028 patients with invasive breast cancer included in this study were followed for a median of 95 months, during which the 8-year LR, IBTR, DDFS, and DFS rates were 2.6%, 3.0%, 93.7%, and 91.3%, respectively. Lymph node involvement, the human epidermal growth factor receptor 2 (HER2) status, and the use of computed tomography (CT) information during boost field planning were identified as significant predictors of LR and IBTR. Notably, use of the surgical scar for tumor bed identification during boost field planning was associated with a higher adjusted risk of LR, compared with the use of CT. By contrast, the neoadjuvant chemotherapy (NAC) was not an independent predictor of LR (hazard ratio of no NAC vs. NAC, 0.63; 95% confidence interval, 0.33-1.19; P = 0.157). In a multivariate analysis, the age at diagnosis, tumor diameter, lymph node involvement, HER2-positive status, and use of CT information during boost field planning were identified as significant factors affecting DFS.Conclusions: The use of CT information during boost field planning could reduce the risk of LR among patients undergoing BCT. Neoadjuvant and adjuvant treatments for breast cancer did not show the significant difference in respect to the outcome of LR.

Fibroepithelial lesions of the breast: a comprehensive morphological and outcome analysis of a large series

AbstractMammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3–249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

Prediction of cervical cancer recurrence using textural features extracted from 18F-FDG PET images acquired with different scanners

ObjectivesTo identify an imaging signature predicting local recurrence for locally advanced cervical cancer (LACC) treated by chemoradiation and brachytherapy from baseline 18F-FDG PET images, and to evaluate the possibility of gathering images from two different PET scanners in a radiomic study.Methods118 patients were included retrospectively. Two groups (G1, G2) were defined according to the PET scanner used for image acquisition. Eleven radiomic features were extracted from delineated cervical tumors to evaluate: (i) the predictive value of features for local recurrence of LACC, (ii) their reproducibility as a function of the scanner within a hepatic reference volume, (iii) the impact of voxel size on feature values.ResultsEight features were statistically significant predictors of local recurrence in G1 (p < 0.05). The multivariate signature trained in G2 was validated in G1 (AUC=0.76, p<0.001) and identified local recurrence more accurately than SUVmax (p=0.022). Four features were significantly different between G1 and G2 in the liver. Spatial resampling was not sufficient to explain the stratification effect.ConclusionThis study showed that radiomic features could predict local recurrence of LACC better than SUVmax. Further investigation is needed before applying a model designed using data from one PET scanner to another.

Endoscopic treatment outcomes of laterally spreading tumors with a skirt (with video)

A "skirt" is a slightly elevated flat lesion with wide pits occasionally observed at the margin of laterally spreading tumors (LSTs). However, the endoscopic treatment outcomes of LSTs with skirts have not been clarified. The aim of this study was to evaluate the endoscopic treatment outcomes of LSTs with skirts. Between February 2006 and March 2014, 996 LSTs were retrospectively examined to assess the clinicopathologic characteristics, procedure time, en bloc resection rate, R0 resection rate, adverse events, and local recurrence rate of endoscopic submucosal dissection (ESD) and of endoscopic resection. Endoscopic treatment was performed in 35 cases of LSTs with skirts (ratio of ESD to endoscopic piecemeal mucosal resection [EPMR], 32:3) and 961 cases of LSTs without skirts (ratio of ESD to EMR to EPMR to polypectomy, 381:275:114:191). LSTs with a skirt were associated with a significantly higher recurrence rate (P<.01). In both ESD and EPMR, LSTs with a skirt were associated with a higher recurrence rate when compared with LSTs without a skirt (odds ratio, 12.7; P= .032, and odds ratio, 12.3; P= .061, respectively). Multivariate analysis demonstrated that the presence of the skirt and piecemeal resection were significant predictors of local recurrence. LSTs with skirts had a significantly higher local recurrence rate after endoscopic treatment compared with LSTs without skirts, especially after EPMR. Therefore, ESD should be recommended as an endoscopic treatment for LSTs with skirts to minimize local recurrence.

Surgical management of primary retroperitoneal tumors – Analysis of a single center experience

BackgroundRetroperitoneal tumors are a rare but diverse group of neoplasms that arise from the retroperitoneum. Local recurrence after surgical resection greatly influenced survival. We aimed to analyze factors affecting outcome after surgery at our institution. Materials and methodsA database was reviewed retrospectively to identify patients who underwent surgery for retroperitoneal tumors from 2007 to 2012. Patient demographics, operative outcomes and tumor variables were recorded. Multivariable analysis was performed to evaluate predictors for overall survival. ResultsA total of 41 cases were treated surgically. The median diameter of tumors was 13.7 cm (2.5 cm–39 cm). In 90% of the cases, macroscopic complete resection was achieved. Twenty-one percent of these cases required en bloc multi-organ resection. Fifty percent developed local recurrence and 15% had distant metastasis during 7-years of follow up. Local recurrence was significantly associated with overall survival and macroscopic incomplete resection was a significant predictor of local recurrence. ConclusionComplete resection of retroperitoneal tumors with oncologically free margins should be the goal at surgery. Microscopic complete resection plays an important role in improving survival.

Lung Adenocarcinoma: Predictive Value of KRAS Mutation Status in Assessing Local Recurrence in Patients Undergoing Image-guided Ablation.

Purpose To establish the relationship between KRAS mutation status and local recurrence after image-guided ablation of lung adenocarcinoma. Materials and Methods This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of 56 primary lung adenocarcinomas in 54 patients (24 men, 30 women; median age, 72 years; range, 54-87 years) treated with percutaneous image-guided ablation and with available genetic mutational analysis. KRAS mutation status and additional clinical and technical variables-Eastern Cooperative Oncology Group (ECOG) status, smoking history, stage at diagnosis, status (new primary or not), history of radiation, history of surgery, prior systemic treatment, modality of ablation, size of nodule, ablation margin, and presence of ground-glass appearance-were recorded and evaluated in relation to time to local recurrence, which was calculated from the time of ablation to the first radiographic evidence of recurrence. Predictors of outcome were identified by using a proportional hazards model for both univariate and multivariate analysis, with death as a competing risk. Results Technical success was 100%. Of the 56 ablated tumors, 37 (66%) were wild type for KRAS and 19 (34%) were KRAS mutants. The 1-year and 3-year cumulative incidences of recurrence were 20% and 35% for wild-type KRAS compared with 40% and 63% for KRAS mutant tumors. KRAS mutation status was a significant predictor of local recurrence at both univariate (P = .05; subdistribution hazard ratio [sHR], 2.32) and multivariate (P = .006; sHR, 3.75) analysis. At multivariate analysis, size (P = .026; sHR, 2.54) and ECOG status (P = .012; sHR, 2.23) were also independent significant predictors, whereas minimum margin (P = .066) was not. Conclusion The results of this study show that there is a relationship between KRAS mutation status and local recurrence after image-guided ablation of lung adenocarcinoma. Specifically, KRAS mutation status of the ablated lesion is a significant predictor of time to local recurrence, independent of size and margin. © RSNA, 2016.

Abstract P3-12-03: Utilizing the genomically adjusted dose (GAD) to personalize radiotherapy in adjuvant breast cancer management

Abstract Background: We have previously validated a multi-gene model of tumor radiosensitivity (RSI) with validation in multiple independent cohorts including breast, rectal, esophageal, head and neck, glioblastoma, and prostate malignancies. Utilizing the linear quadratic model and RSI, we derived an expression for the genomically adjusted dose (GAD) to model radiation dose effect for individual patients. Methods: As RSI models the surviving fraction of cells at 2 Gy (SF2), we are able to derive a patient specific alpha. These terms were used in the linear quadratic model to calculate a GAD to model radiation effect and its association with local control. A higher GAD implies a higher predicted radiation therapy effect. Clinical and array-based gene expression were obtained from 75 ER negative patients from the Netherlands Cancer Institute (NKI) and the Institut Curie treated with breast conservation therapy. Results: Median follow-up for all patients was 10 years with a median age of 42 years (range: 23-50 years). Adjuvant radiation dose to the whole breast was 50 Gy (range: 45-55 Gy). When assessing local recurrence on multivariate analysis, we found GAD to be a significant predictor of local recurrence when dichotomized at the median (GAD-low vs GAD-high Hazard Ratio (HR) 4.5; 95% CI 1.7-13.5; p=0.0031). GAD was also significant per unit change (HR 0.91; 95% CI 0.83-0.99; p=0.021). We then modeled GAD for an escalated dose up to 60 Gy and found an additional 48% of GAD-low patients could achieve a GAD-high with dose escalation. Conclusions: We found GAD to be significantly correlated with local control following breast conservation therapy. Modeling dose escalation with GAD, we identified a select population of patients whom we hypothesize may benefit from genomically guided increased dose in the adjuvant setting. This population may represent a cohort for future clinical trial enrollment. Citation Format: Ahmed KA, Venkat PS, Scott JG, Diaz RJ, Fulp WJ, Torres-Roca JF. Utilizing the genomically adjusted dose (GAD) to personalize radiotherapy in adjuvant breast cancer management. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-03.

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). The combined molecular subtype-RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy-based decisions in breast cancer.

High tumor volume and local recurrence following surgery in osteosarcoma: A retrospective study.

Background:Osteosarcoma is a high grade malignant, osteoid forming, primary bone tumor affecting the metaphysis of long bones. Local recurrence (LR) in osteosarcomas is a sinister. Theoretically, a high tumor volume at the time of presentation will limit surgical margins, involve vital neurovascular bundles and show poor response to chemotherapy thereby causing high rates of amputations (as against limb salvage surgery) and should be associated with poor survival rates. This study evaluated objectively if high tumor volume is a significant predictor of local recurrence (LR) in operated cases of osteosarcomas.Materials and Methods:Operated cases of osteosarcoma (presenting to the Orthopedic outpatient or the Medical Oncology outpatient between January 1, 2004 and January 1, 2011 were included in the study. Their preoperative clinical data and investigations along with the operative notes were traced from the medical/departmental records. Details of chemotherapy received in the neo-adjuvant and postoperative periods were noted. Besides, all demographic data were also noted. Tumor volume was calculated using the available magnetic resonance images using the formula: ([π/6] × length × width × depth). Post data extraction, patients were divided in two groups, Groups I (without LR) and Group II (with LR).Results:A total of 95 cases of biopsy proven osteosarcomas were identified. Of which 64 were male and 31 females. There were 15 (15.8%) local recurrences. 71% (57/80) patients without LR fell in the age group of 10-20 years, while 66% (10/15) patients with LR were in the age group of 10-20 years. Limb salvage surgery was done in 81.05% (77/95) patients while a total of 18 patients underwent amputation. Of the 80 cases in Group I (without LR), 40 (50%) patients had tumor volume >200 c.c., 30 patients (37.5%) had tumor volume between 50 and 200 c.c. while only 10 patients had tumor volumes <50 c.c. This was in contrast to the tumor volume noted in Group II (with LR) of 15 patients where 8 patients had a tumor volume between 50 and 200 c.c., five had bigger tumor volumes of >200 c.c. and only two patients were smaller in size, with a tumor volume <50 c.c. The mean tumor volume in the group without LR was 406.74 ± 771.67 c.c. as compared with 195.77 ± 226.8 c.c. in the group with local recurrence. Using Mann-Whitney test, the difference between the two groups was found to be statistically insignificant (P = 1.403).Conclusions:We conclude that high tumor volume is not a significant predictor of LR in osteosarcomas thus patients with high tumor masses should not be denied limb salvage. However, we recommend that the decision on attempting limb salvage should not only be based on the tumor volume alone.

Breast-Conserving Therapy for Triple-Negative Breast Cancer

The aggressive triple-negative phenotype of breast cancer (negative for estrogen and progesterone receptors and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 [ERBB2] [formerly human epidermal growth factor receptor 2 (HER2)]) is considered by some investigators to be a relative contraindication to breast-conserving therapy. To compare outcomes of breast-conserving therapy for patients with triple-negative breast cancer (TNBC) with those of patients with the luminal A, luminal B, and ERBB2 subtypes. Prospective database review at an academic tertiary medical center with a designated breast cancer center. We included 1851 consecutive patients ages 29 to 85 years with stages I to III invasive breast cancer who underwent breast-conserving therapy at a single institution from January 1, 2000, through May 30, 2012. Of these patients, 234 (12.6%) had TNBC; 1341 (72.4%), luminal A subtype; 212 (11.5%), luminal B subtype; and 64 (3.5%), ERBB2-enriched subtype. Breast-conserving therapy. The primary outcome measure was local recurrence (LR). Secondary outcome measures included regional recurrence, distant recurrence, and overall survival. RESULTS Triple-negative breast cancer was associated with younger age at diagnosis (56 vs 60 years; P = .001), larger tumors (2.1 vs 1.8 cm; P < .001), more stage II vs I cancer (42.1% vs 33.6%; P = .005), and more G3 tumors (86.4% vs 28.4%; P < .001) compared with the non-TNBC subtypes. Multivariable analysis showed that TNBC did not have a significantly increased risk of LR compared with the luminal A (hazard ratio, 1.4 [95% CI, 0.6-3.3]; P = .43), luminal B (1.6 [0.5-5.2]; P = .43), and ERBB2 (1.1 [0.2-5.2]; P = .87) subtypes. Only tumor size was a significant predictor of LR (hazard ratio, 4.7 [95% CI, 1.6-14.3]; P = .006). Predictors of worse overall survival included tumor size, grade, and stage and TNBC subtype. Breast-conserving therapy for TNBC is not associated with increased LR compared with non-TNBC subtypes. However, the TNBC phenotype correlates with worse overall survival. Breast-conserving therapy is appropriate for patients with TNBC.

Patterns of recurrence after stereotactic radiosurgery for treatment of meningiomas

The purpose of this study was to evaluate patterns of failure after stereotactic radiosurgery (SRS) for meningiomas and factors that may influence these outcomes. Based on a retrospective chart review, 279 patients were treated with SRS for meningiomas between January 1999 and March 2011 at Wake Forest Baptist Health. Disease progression was determined using serial imaging, with a minimum follow-up of 6 months (median 34.2 months). The median margin dose was 12.0 Gy (range 8.8-20 Gy). Local control rates for WHO Grade I tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and 5 years, respectively. Tumors without pathological grading had local control rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local recurrences, 63.1% were classified as marginal (within 2 cm of treatment field). The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%, respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for Grade II/III tumors. Tumors without pathological grading had distant failure rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon analysis revealed that multifocal disease (p < 0.001) and high-grade histology (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence. Additionally, male sex was a significant predictor of distant recurrence (p = 0.04). Multivariate analysis also showed that doses greater than or equal to 12 Gy were associated with improved local control (p = 0.015). In this patient series, 12 Gy was the minimum sufficient margin dose for the treatment of meningiomas. Male sex is a risk factor for distant failure, whereas high-grade histology and multifocal disease are risk factors for local failure.

Pathologically Determined Tumor Volume vs Pathologic T Stage in the Prediction of Outcome After Surgical Treatment of Oropharyngeal Squamous Cell Carcinoma

Traditional prognostic models for squamous cell carcinoma of the head and neck are based on the TNM staging system. However, there is growing evidence that tumor volume (TV) may be a more accurate predictor of outcome. To determine whether pathologic TV (pTV) in patients with oropharyngeal squamous cell carcinoma treated surgically is a more significant predictor of outcome compared with pathologic tumor (pT) stage. Review of patients whose treatment was managed between January 1, 1985, and December 2005 at a US tertiary referral cancer center. The participants included 159 patients who had undergone primary surgery for oropharyngeal squamous cell carcinoma and had 3 dimensions reported on histopathologic testing. The pTV was calculated as the product of the 3 dimensions expressed in cubic centimeters. For comparison of pT stage with pTV in outcome prediction, concordance indexes were generated using the bootstrap method (n = 1000) to quantify the predictive accuracy of recurrence and survival outcomes. Concordance indexes were then compared and a significant difference was considered when P < .05. The median age of the patients was 59 years (range, 22-84 years) and 106 were male (67%). Sites of the tumors were base of the tongue (86 patients [54%]), tonsil (48 [30%]), soft palate (24 [15%]), and posterior pharyngeal wall (1 [1%]). The median follow-up time was 64 months (range, 1-272 months). The median tumor volume was 6.8 cm3 (range, 0.1-162.5 cm³). Pathologic TV was a significant predictor of disease-specific mortality. Unlike pT stage, pTV was a significant predictor of local recurrence, regional recurrence, and distant recurrence. Comparison of concordance indexes showed that pTV was a significantly better predictor of disease-specific mortality, local recurrence, and distant recurrence (all P < .05). Pathologic TV outperforms pT stage in the prediction of outcome following surgical treatment of oropharyngeal cancer. Tumor volume should be considered in the design of prospective surgical trials.

An Analysis of Factors Related to Recurrence of Myxofibrosarcoma

Myxofibrosarcoma is clinically characterized by a high frequency of local recurrence after surgery. To improve the clinical outcome of patients with myxofibrosarcoma, it is imperative to control any postsurgical local recurrence. In this study, we performed a retrospective clinicopathologic analysis of 100 consecutive patients with myxofibrosarcoma to identify factors related to poor prognosis. All of the patients had been diagnosed, and had undergone surgery at the National Cancer Center Hospital between 1999 and 2008. At the initial visit to our hospital, 64 patients had primary myxofibrosarcoma, whereas 36 had undergone primary unplanned resection at other facilities. Of the 36 patients, 11 consulted our hospital before recurrence and 25 did so after recurrence. A histologically positive margin after surgery was evident in 28% of the cases overall. The estimated 5-year recurrence-free survival rate was 74.8%. Univariate analysis showed that primary unplanned resection at another facility (P = 0.0001) and a histologically positive margin (P = 0.0224) were significant predictors of local recurrence. When these two factors were subjected to multivariate analysis, only primary unplanned resection at another facility was significantly correlated with the estimated recurrence-free survival rate (P = 0.0011). Primary unplanned resection was also significantly related to the 5-year disease-free survival rate (P = 0.0401). Our findings indicate that primary unplanned resection at a non-referral hospital is the most important risk factor related to poor prognosis of myxofibrosarcoma. Accurate diagnosis and adequate initial surgery are most important factors for improving the clinical outcomes of myxofibrosarcoma.

Prognostic Value of Lymph Node Ratios in Node Positive Rectal Cancer Treated with Preoperative Chemoradiation

To investigate the impact of the lymph node ratio (LNR) on the prognosis of patients with locally advanced rectal cancer undergoing pre-operative chemoradiation. Clinicopathologic and follow up data of 128 patients with stage III rectal cancer who underwent curative resection from 1996 to 2007 were reviewed. The patients were divided into two groups according to the lymph node ratio: LNR ≤ 0.2 (n=28), and >0.2 (n=100). Kaplan-Meier and the Cox proportional hazard regression models were used to evaluate the prognostic effects according to LNR. Median numbers of lymph nodes examined and lymph nodes involved by tumour were 10.3 (range 2-28) and 5.8 (range 1-25), respectively, and the median LNR was 0.5 (range, 0-1.6). The 5-year survival rate significantly differed by LNR (≤ 0.2, 69%; >0.2, 19%; Log-rank p value < 0.001). LNR was also a significant prognostic factor of survival adjusted for age, sex, post-operative chemotherapy, total number of examined lymph nodes, metastasis and local recurrence (≤ 0.2, HR=1; >0.2, HR=4.8, 95%CI=2.1-11.1) and a significant predictor of local recurrence and distant metastasis during follow-up independently of total number of examined lymph node. Total number of examined lymph nodes and LNR were significant prognostic factors for survival in patients with stage III rectal cancer undergoing pre-operative chemoradiotherapy.