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Background: Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes., Methods: A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome., Results: At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R., Discussion: Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.

Background: The practice of salvaging recurrent rectal cancer has evolved. The aim of this study was to define the evolving salvage potential over time among patients with locally recurrent disease, and to identify durable determinants of long-term success., Methods: The study included consecutive patients with recurrent rectal cancer undergoing multimodal salvage with curative intent between 1988 and 2012. Predictors of long-term survival were defined by Cox regression analysis and compared over time. Re-recurrence and subsequent treatments were evaluated., Results: After multidisciplinary evaluation of 229 patients, salvage therapy with curative intent included preoperative chemotherapy and/or radiotherapy (73·4 per cent; with 41·3 per cent undergoing repeat pelvic irradiation), surgical salvage resection with or without intraoperative irradiation (36·2 per cent), followed by postoperative adjuvant chemotherapy (38·0 per cent). Multivisceral resection was undertaken in 47·2 per cent and bone resection in 29·7 per cent. The R0 resection rate was 80·3 per cent. After a median follow-up of 56·5 months, the 5-year overall survival rate was 50 per cent in 2005-2012, markedly increased from 32 per cent in 1988-1996 (P = 0·044). Long-term success was associated with R0 resection (P = 0·017) and lack of secondary failure (P = 0·003). Some 125 patients (54·6 per cent) developed further recurrence at a median of 19·4 months after salvage surgery. Repeat operative rescue was feasible in 21 of 48 patients with local re-recurrence alone and in 17 of 77 with distant re-recurrence, with a median survival of 19·8 months after further recurrence., Conclusion: The long-term salvage potential for recurrent rectal cancer improved significantly over time, with the introduction of an individualized treatment algorithm of multimodal treatments and surgical salvage. Durable predictors of long-term success were R0 resection at salvage operation, avoidance of secondary failure, and feasibility of repeat rescue after re-recurrence., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Radiation therapy is used increasingly as a component of multidisciplinary treatment for many solid tumors. One complication of such treatment is the development of radiation-associated sarcoma (RAS). Undifferentiated pleomorphic sarcoma (UPS), previously termed "malignant fibrous histiocytoma" (MFH) is the most common histologic subtype of RAS. This study investigated the clinical outcomes for patients with radiation-associated UPS (RA-UPS/MFH)., Methods: The study identified 1068 patients with UPS/MFH treated at the authors' institution. Patient and tumor factors were collected and compared. Regression analysis was performed to identify independent predictors of survival. A matched-cohort survival and recurrence analysis was performed for radiation-associated and sporadic UPS/MFH., Results: The findings showed that RA-UPS/MFH comprised 5.1 % of the UPS population. The median latency to the development of RA-UPS/MFH was 9.3 years. The 5-year disease-specific survival (DSS) was 52.2 % for patients identified with RA-UPS/MFH (n = 55) compared with 76.4 % for patients with unmatched sporadic UPS/MFH (n = 1,013; p < 0.001). A matched-cohort analysis also demonstrated that the 5-year DSS was significantly worse for RA-UPS/MFH (52.2 vs 73.4 %; p = 0.002). Furthermore, higher local recurrence rates were observed for patients with RA-UPS/MFH than for patients with sporadic lesions (54.5 vs 23.5 %; p < 0.001). Radiation-associated status and incomplete resection were identified as independent predictors of local recurrence., Conclusion: This study demonstrated worse clinical outcomes for patients with RA-UPS/MFH than for patients with sporadic UPS/MFH. Local recurrence was significantly higher for patients with RA-UPS/MFH, suggesting a unique tumor biology for this challenging disease.

The purpose of this study was to determine the outcome of surgery for patients with recurrent gastric or gastroesophageal cancer. We queried records from 7,459 patients who presented with gastric or gastroesophageal cancer to our institution from 1973 through 2005 to identify those for whom resection of recurrent disease had been attempted. We assessed the associations between various clinicopathologic factors and resectability with logistic regression analysis and between clinicopathologic factors and overall survival (OS) with the Cox proportional hazards model. Sixty patients underwent attempted resection for recurrent cancer. In 31 cases (52%), recurrent disease proved unresectable at laparotomy. Factors associated with the ability to undergo re-resection included neoadjuvant treatment prior to initial resection [odds ratio (OR) 12.2, 95% confidence interval (CI) 1.9-75.6] and having an isolated local recurrence (OR 5.1, 95% CI 1.3-20.5). Of the 29 patients who underwent re-resection, 14 required adjacent organ resection, and 6 required interposition grafting. Three- and 5-year OS rates for all 60 patients were 21% and 12%, respectively; median follow-up time was 23 months. Median OS for patients undergoing resection was 25.8 months (95% CI 17.1-49.8) versus 6.0 months (95% CI 4.0-10.5) for unresectable patients (P < 0.001). Initial tumor location at the gastroesophageal junction was associated with diminished OS [hazard ratio (HR) 2.8, 95% CI 1.2-6.5] and ability to undergo resection of recurrence was associated with improved OS (HR 0.2, 95% CI 0.1-0.6). We conclude that surgical resection of select patients with recurrent gastric or gastroesophageal cancer can result in improved OS but often requires adjacent organ resection or interposition graft placement.

Purpose: Few biologic markers have been studied as prognostic factors in recurrent rectal carcinoma patients. We sought to determine the influence of clinical, pathologic, and biologic (p53, bcl-2, and ki-67) variables on survival after curative resection of locally recurrent rectal cancer., Methods: Retrospective review of patients with locally recurrent rectal cancer who received surgery with curative intent., Results: From 1988 to 1998, 134 patients with locally recurrent rectal cancer underwent operative exploration. Curative resection was performed in 85 patients. Median follow-up was 43 (range, 1.3-149) months. On multivariate analysis, negative predictors of overall survival included an elevated carcinoembryonic antigen level (P=0.02; hazard ratio 2.41; 95 percent confidence interval, 1.19-4.89) and an R1 resection margin (P = 0.01; hazard ratio, 2.81; 95 percent confidence interval, 1.27-6.21). In 26 patients for whom biologic variables were available, p53, bcl-2, and ki-67 did not significantly impact disease-specific survival or overall survival. Five-year disease-specific survival, overall survival, and pelvic control rates were 46, 36, and 51 percent respectively. Of the 50 patients who relapsed, time to second local recurrence was longer than time to development of metastasis (median, 16.5 vs. 9 months). Median survival for patients with metastatic recurrence was 26.l vs. 41.5 months for those with a subsequent local recurrence alone., Conclusions: Approximately two-thirds of patients with locally recurrent rectal cancer can be resected for cure. Preoperative carcinoembryonic antigen and an R0 resection margin were the only significant predictors of overall survival. p53, bcl-2, and ki-67 did not impact survival outcomes.

Purpose: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies., Patients and Methods: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease., Results: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005)., Conclusion: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.

Reports of recurrent malignant disease developing at laparoscopic port sites has created considerable controversy among surgeons. Many have implicated the technique of laparoscopy as a cause of metastases and this has led to condemnation of laparoscopy in malignant disease by many surgeons. A review of the case reports, as well as animal studies, reveals the problem to be considerably more complex. Based on experimental models, reported cases, and our experience at the University of Texas M. D. Anderson Cancer Center, we have arrived at some substantive conclusions regarding this phenomenon. Port site recurrences (PSRs) after laparoscopy for malignant disease can occur as the only site of recurrence, but this is an extremely rare event, and the incidence does not appear to be significantly different from the development of wound recurrences after open laparotomy for malignancy. It is likely that port site recurrences reflect the underlying biology of the malignant disease, rather than an effect of the technique of laparoscopy.

Purpose: The use of further radiotherapy among patients with soft tissue sarcoma that recurs in a previously irradiated area is controversial. Presented is a review of our 7-year experience with brachytherapy for recurrent soft tissue sarcoma., Methods: A retrospective review was performed of 26 patients who underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated field. After-loading brachytherapy catheters were placed at the time of surgical extirpation of the sarcoma within a single-plane implant by use of 1-cm intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until the fifth to seventh postoperative day to allow initial wound healing. The prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and the dose was specified at 0.5 cm from the plane of the implant. The anatomic locations treated included lower extremity (N = 10), upper extremity (N = 7), trunk (N = 7), and head and neck (N = 2)., Results: Total tumor extirpation, confirmed by negative frozen section margins, was accomplished in all cases. The mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy +/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue transfer flap was placed over the bed of resection in 13 cases. Complications occurred in five patients including, three with wound breakdown, one with osteonecrosis, and with neuralgia. Operative intervention was required in four of the five patients with complications; each of the patients requiring operative intervention for wound-related complications had undergone primary wound closure without tissue transfer. Recurrence of disease occurred in 13 patients: nine local and four distant metastases. The median follow-up was 16 months (range, 2 to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease-free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%, respectively., Conclusion: Re-irradiation of recurrent soft tissue sarcoma by brachytherapy in conjunction with resection can be performed with acceptable complication rates. Local control can be achieved for the majority of patients who would otherwise require more radical surgical procedures.

Background: Laparoscopy in patients with intra-abdominal malignancy remains controversial. This study evaluates the incidence of tumor recurrence at the port site after laparoscopy in patients with intra-abdominal malignancy., Methods: The medical records of all patients with nongynecologic malignancies who underwent laparoscopic procedures between May 1, 1990, and June 30, 1996, at the University of Texas M.D. Anderson Cancer Center were reviewed. Data on extent of tumor, histologic findings, primary location, procedures performed, and complications were recorded., Results: During this time, 533 patients with known intra-abdominal malignancies underwent laparoscopy. Mean follow-up time was 13.2 +/- 0.5 months (range 1 to 71 months; median 10.6 months). Four recurrences at the port site were identified (0.8%). Three of these patients had advanced intra-abdominal disease at the time of laparoscopy; 1 patient without advanced disease at the time of laparoscopy had a recurrence at the port site as the only site of recurrent disease (0.19%). The incidence of port site recurrences among patients with advanced intra-abdominal disease at the time of laparoscopy (3/71) was significantly greater than the risk of development of a recurrence at the port site among patients without advanced intra-abdominal disease at the time of laparoscopy (1/462; P < .0003, by chi-square analysis)., Conclusion: Recurrence at the port site is very rare. When implantation at the port site does occur, it is most commonly associated with advanced intra-abdominal disease.

Background: The local recurrence (LR) rate with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) has been reported as comparable to the LR rate after conventional mastectomy. However, limited data are available on the prognostic significance and management of LR following SSM., Methods: A prospective database maintained at the University of Texas M. D. Anderson Cancer Center identified 437 SSMs performed for 372 invasive T1/T2 breast cancers between 1986 and 1993., Results: Twenty-three LRs were identified, with a LR rate of 6.2% (23/372). Twenty-two of these (96%) presented as palpable skin-flap masses. The median time to recurrence was 25 months (range, 3 to 98 months). Fourteen patients were treated with a combination of surgery and systemic therapy. Resection of the reconstructed breast was performed in only three patients. Complete local control of the recurrent disease was achieved in 17 patients (74%). Nine patients (39%) developed distant metastatic disease. At a median follow-up of 26 months, 14 of 23 patients (61%) are alive without evidence of disease, and 7 (30%) have died from breast cancer., Conclusions: Because LR rate with SSM is low and likelihood of local control and survival is high, SSM and IBR is an acceptable treatment option for early stage breast cancer.

Background: The role of elective contralateral mastectomy (ECM) in women with early-stage breast cancer who elect or require an ipsilateral mastectomy and desire immediate bilateral breast reconstruction (IBR) is an intellectual and emotional dilemma for both patient and physician. In an attempt to clarify the rationale for this approach, we reviewed our experience with ECM and IBR and evaluated operative morbidity, the incidence of occult contralateral breast cancer, and patterns of recurrence., Patients and Methods: We retrospectively reviewed the records of 155 patients with primary unilateral breast cancer (stage 0, I, or II) and negative findings on physical and mammographic examinations of the contralateral breast who underwent ipsilateral mastectomy and simultaneous ECM with IBR between 1987 and 1995., Results: The median age of the patients was 46 years (range, 25 to 69 years). Clinical stage at diagnosis was stage 0, I, and II in 19.4%, 54.2%, and 26.4% of patients, respectively. Factors likely to influence the use of ECM were family history of breast cancer in first-degree relatives (30%), any family history of breast cancer (56%), difficulty anticipated in contralateral breast surveillance (48%), associated lobular carcinoma in situ (23%), multicentric primary tumor (28%), significant reconstructive issues (14%), and failure of mammographic identification of the primary tumor (16%). Skin-sparing mastectomies were performed in 81% of patients. Overall, 70% of patients underwent reconstruction using autogenous tissue transfer. Reoperations for suspected anastomotic thrombosis were performed in seven patients. Two patients experienced significant partial or complete flap loss. Histopathologic findings in the ECM specimen were as follows: benign, 80% of patients; atypical ductal hyperplasia, 12% of patients; lobular carcinoma in situ, 6.5% of patients; ductal carcinoma in situ, 2.7% of patients; and invasive carcinoma, 1.3% of patients. Eighteen patients (12%) had evidence of locoregional or distant recurrences, with a median follow-up of 3 years. In one patient (0.6%), invasive ductal carcinoma developed on the side of the elective mastectomy., Conclusions: The use of ECM and IBR cannot be justified if the only oncologic criterion considered is the incidence of occult synchronous contralateral disease. However, in a highly selected population of young patients with a difficult clinical or mammographic examination and an increased lifetime risk of developing a second primary tumor, ECM and IBR is a safe approach.

Background: The management of locally recurrent extremity soft tissue sarcoma remains challenging. This study was undertaken to evaluate the long-term outcome after therapy for isolated locally recurrent soft tissue sarcoma (STS) of the extremity., Methods: Between January 1, 1980, and December 31, 1990, 52 patients were treated at The University of Texas M. D. Anderson Cancer Center for locally recurrent extremity STS. The records of the subset of these patients (n = 36) with isolated local recurrence were examined to document clinicopathologic and treatment factors and to evaluate outcome using the end points of local recurrence-free, recurrence-free, and overall survival., Results: Limb-sparing conservative surgery was possible in 24 patients (75%). Twelve (33%) of 36 patients were treated by surgery alone, 23 patients (64%) were treated with combined modality therapy (surgery plus radiation and/or chemotherapy), and 1 patient had radiotherapy only. Sixteen (44%) of 36 patients had no further recurrence of any type at a median follow-up of 58 months (range, 4 to 173 months). The 5-year actuarial local recurrence-free, recurrence-free, and overall survival rates were 72%, 45%, and 77%, respectively., Conclusions: Limb-sparing conservative surgery is possible in the majority of patients with isolated locally recurrent STS. Durable local control can be established with individualized local treatment strategies. These results support aggressive multimodality limb-sparing treatment approaches for these patients.