Meena Bedi

Multimodality management of metastatic patients with soft tissue sarcomas may prolong survival.

Objectives:Patients who develop metastatic disease from soft tissue sarcoma have a poor prognosis. The purpose of this study was to identify metastatic survival rates and identify prognostic variables that predict for these outcomes. Methods:Between 2000 and 2010, 182 patients with stage I to IV primary soft tissue sarcomas of the extremity and trunk were treated with multimodality treatment. Fifty-five patients developed or presented with metastasis. We retrospectively analyzed prognostic factors for metastatic survival. Metastatic survival between groups was compared with the log-rank test. Survival curves were estimated by Kaplan-Meier plots. Multivariate analysis was performed using the Cox proportional hazards model. Results:Median follow-up was 3.1 years. Median metastatic survival was 24.2 months. Median metastatic survival in those undergoing multimodality therapies was 40 versus 22 months in those receiving single modality treatments. In single predictor Cox models, age, stage, number of lung metastases, location of metastases, and primary disease were significant for metastatic survival. On multivariate analysis, number of pulmonary metastases, histology, stage, and location of primary disease predicted for metastatic survival. Patients who had pulmonary-only disease had improved metastatic survival versus those that had extrapulmonary with or without pulmonary metastatic disease (38 vs. 15 mo). Patients who had ⩽5 pulmonary metastasis had improved metastatic survival versus those that had >5 pulmonary lesions (55 vs. 22 mo). Conclusions:This analysis shows that >5 pulmonary metastasis, malignant fibrous histiocytoma histology, stage III disease, and proximal lower extremity sarcomas are associated with decreased metastatic survival. Moreover, aggressive multimodality management of metastatic disease may prolong metastatic survival.

Prognostic variables in patients with primary soft tissue sarcoma of the extremity and trunk treated with neoadjuvant radiotherapy or neoadjuvant sequential chemoradiotherapy

BackgroundNeoadjuvant radiotherapy (NRT) is an effective strategy to treat soft tissue sarcomas (STS). However, the role of neoadjuvant chemoradiotherapy (NCRT) remains to be determined.MethodsFrom May 1999 to July 2010, 112 patients with localized STS of the extremity and trunk who were treated with NRT or NCRT followed by surgery were retrospectively reviewed. Clinical outcomes including overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS) were calculated using Kaplan-Meier survival analyses. Prognostic variables were determined by univariate (UVA) and multivariate analyses (MVA).ResultsMedian follow-up was 37 months. Median RT dose was 50 Gy. Forty-nine patients received NCRT. Overall limb-preservation rate was 99% and local control was 97%. The estimated 3-year OS, DFS, and DMFS were 86%, 68%, and 72%, respectively. Age was the only variable to predict for OS, DFS and DMFS on UVA. Age ≥ 70 predicted for poor OS, stage III disease predicted for poor DFS and DMFS, and the addition of chemotherapy predicted for improved DMFS on MVA.ConclusionsExcellent rates of local control and limb-preservation were observed in patients with primary STS treated with neoadjuvant therapy followed by surgery. Neoadjuvant sequential chemotherapy followed by radiotherapy may be considered for young patients with stage III STS.

Neoadjuvant radiotherapy for retroperitoneal sarcoma: A systematic review.

The multi‐modal treatment of retroperitoneal sarcoma has seen increased use of neoadjuvant radiation. However, its effect on local recurrence and survival remain controversial. We aimed to synthesize and evaluate the literature.

Elective Lymph Node Irradiation With Intensity-Modulated Radiotherapy: Is Conventional Dose Fractionation Necessary?

PURPOSE Intensity-modulated radiation therapy (IMRT) is the standard of care for head-and-neck cancer (HNC). We treated patients with HNC by delivering either a moderate hypofractionation (MHF) schedule (66 Gy at 2.2 Gy per fraction to the gross tumor [primary and nodal]) with standard dose fractionation (54-60 Gy at 1.8-2.0 Gy per fraction) to the elective neck lymphatics or a conventional dose and fractionation (CDF) schedule (70 Gy at 2.0 Gy per fraction) to the gross tumor (primary and nodal) with reduced dose to the elective neck lymphatics. We analyzed these two cohorts for treatment outcomes. METHODS AND MATERIALS Between November 2001 and February 2009, 89 patients with primary carcinomas of the oral cavity, larynx, oropharynx, hypopharynx, and nasopharynx received definitive IMRT with or without concurrent chemotherapy. Twenty patients were treated using the MHF schedule, while 69 patients were treated with the CDF schedule. Patient characteristics and dosimetry plans were reviewed. Patterns of failure including local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), overall survival (OS), and toxicities, including rate of feeding tube placement and percentage of weight loss, were reviewed and analyzed. RESULTS Median follow-up was 31.2 months. Thirty-five percent of patients in the MHF cohort and 77% of patients in the CDF cohort received chemotherapy. No RR was observed in either cohort. OS, DFS, LR, and DM rates for the entire group at 2 years were 89.3%, 81.4%, 7.1%, and 9.4%, respectively. Subgroup analysis showed no significant differences in OS (p = 0.595), DFS (p = 0.863), LR (p = 0.833), or DM (p = 0.917) between these two cohorts. Similarly, no significant differences were observed in rates of feeding tube placement and percentages of weight loss. CONCLUSIONS Similar treatment outcomes were observed for MHF and CDF cohorts. A dose of 50 Gy at 1.43 Gy per fraction may be sufficient to electively treat low-risk neck lymphatics.

Minimally invasive local treatments for bone and pulmonary metastases.

Surgery and chemotherapy have historically been the mainstay of treatment in patients with metastatic disease. However there are many alternative therapies available to relieve the symptoms and morbidity of metastases. In this paper, we review the role and highlight the advantages of minimally invasive techniques employed in patients with pulmonary and bone metastases.

Is long-term survival possible after margin-positive resection of retroperitoneal sarcoma (RPS)?

For various reasons, some patients undergo a gross margin positive resection (R2) leading to a dilemma in care. We hypothesized that there is a subset of patients who have long‐term survival (LTS, ≥5 years) after R2 resection for retroperitoneal sarcoma (RPS).

Tumor Increase on MRI after Neoadjuvant Treatment is Associated withGreater Pathologic Necrosis and Poor Survival in Patients with Soft TissueSarcoma

Purpose: MRI is often used to evaluate sarcoma response to neoadjuvant treatment, however its role to predict for pathologic response and survival is unclear. Methods and materials: From 2003-2010, 116 patients with STS were treated with neoadjuvant therapy (NAT). 62 patients who had an MRI before and after radiotherapy were analyzed. Radiographic change was correlated with survival and necrosis and fibrosis on pathology. ROC curve analysis was used to assess change in volume that best predicted for pathological necrosis. Results: Median follow-up was 33 months. There was median tumor volume decrease of 15.08 cm3 after treatment. Increase in tumor size and volume was associated with greater necrosis (p<0.03, p=0.001, respectively) and less fibrosis (p<0.001) on pathology. High-grade tumors had more necrosis (p<0.001) and comprised the majority of patients with tumor increases following NAT (88%). Tumor increase of at least 66% predicted for ≥ 70% necrosis with 94% specificity. The 3-year OS was 65% vs. 93% in patients with a decrease in size and volume (p=0.004). In tumors with ≥ 70% necrosis, the 3-year OS was 38% vs. 91% if necrosis was <70% (p<0.001). Conclusions: MR-based tumor increase following NAT was associated with greater % necrosis and less fibrosis on pathology. This tumor increase was more likely high-grade and associated with worse survival.

Multispectral diffusion-weighted imaging near metal implants

The need for diffusion‐weighted‐imaging (DWI) near metallic implants is becoming increasingly relevant for a variety of clinical diagnostic applications. Conventional DWI methods are significantly hindered by metal‐induced image artifacts. A novel approach relying on multispectral susceptibility artifact reduction techniques is presented to address this unmet need.

Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results.

PURPOSE Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume-to-planning target volume (CTV-to-PTV) margin. METHODS AND MATERIALS Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Students t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. RESULTS The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. CONCLUSIONS The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.

The effect of smoking and major vein resection on post-therapy lymphedema in soft tissue sarcomas treated with neoadjuvant radiation and limb-salvage surgery.

Background:Neoadjuvant therapy with radiation +/− chemotherapy is an accepted management for soft tissue sarcomas (STS). The incidence of post-therapy lymphedema is around 30%. The purpose of this study was to identify variables that predict for post-therapy lymphedema. Methods:From 2000 to 2010, 132 patients with STS were treated with neoadjuvant radiation +/− chemotherapy followed by resection. Patient variables and treatment outcomes were reviewed. Presence of lymphedema was determined by the treating physician. The Fisher exact test was used for univariate analysis and logistic regression was used for multivariate analysis. Results:Median follow-up was 3.1 years. Of the lower extremity STS, major veins were sacrificed in 34% of patients. Lymphedema occurred in 22.4% of patients. Smoking negatively predicted for lymphedema on univariate analysis (P=0.007), and sacrifice of a major vein was associated with an increased risk of lymphedema (P=0.02). On multivariate analysis, smoking (P=0.02, odds ratio 0.31) negatively predicted for and sacrifice of a major vein (P=0.03, odds ratio 2.7) positively predicted for lymphedema. Conclusions:There may be an association between smoking and decrease post-therapy lymphedema. Also, patients who undergo resection of a major vein seem to be more prone to post-therapy lymphedema.