Concomitant Distant Metastases Research Articles

Clinical characteristics and long-term outcomes for parapharyngeal metastases of well-differentiated thyroid cancer during 131 I therapy and follow-up.

Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSSrates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.

Overall Survival of Breast Cancer Patients With Locoregional Failures Involving Internal Mammary Nodes

PurposeInternal mammary node recurrence after definitive breast cancer treatment is poorly characterized, with limited data to guide clinical management. The aim of this study was to analyze the outcomes of patients with recurrent breast cancer involving internal mammary nodes to understand their natural history and determine prognostic factors associated with improved overall survival. Methods and MaterialsWe performed a retrospective analysis of 553 patients with recurrent breast cancer and identified 161 patients with radiographic evidence of locoregional recurrence as a first event. A total of 67 patients (42%) were identified with internal mammary involvement. Median follow-up times were 76 months from date of initial diagnosis and 30 months from date of recurrence. ResultsOf the 67 patients identified with internal mammary node failures, 10 (15%) presented with isolated recurrence, 14 (21%) presented with other sites of locoregional disease, and 43 (64%) presented with concomitant distant metastases. Median overall survival was 2.5 years and significantly associated with extent of disease (P < .0001). On multivariable analysis, concomitant distant metastases, inflammatory breast cancer, and triple negative histologic type were associated with worse overall survival, whereas salvage radiation therapy was associated with improved overall survival. Among the 10 patients with isolated internal mammary node failures, median progression-free survival was 6.0 years and salvage therapy with surgery, radiation, and chemotherapy were associated with the best outcomes. ConclusionsPatients with isolated internal mammary node recurrences achieved long-term survival with aggressive therapies, and salvage radiation therapy was associated with improved survival.

Serosal invasion is a strong prognostic factor for hepatocellular carcinoma after hepatectomy.

The clinical impact of serosal invasion by hepatocellular carcinoma (HCC) remains unclear. This study aimed to clarify the significance of serosal invasion as a prognostic factor for patients who underwent hepatectomy for HCC. This retrospective study investigated patients who underwent hepatectomy for HCC between October 2003 and September 2016 in Ehime University Hospital (Toon, Japan). A total of 161 cases were enrolled after excluding cases of concomitant distant metastasis, macroscopic tumor remnant, mixed HCC, and rehepatectomy. We classified these 161 patients into groups with serosal invasion detected (S[+]) and serosal invasion undetected (S[-]). We compared patient characteristics, perioperative data, pathological findings, and prognosis between S(+) and S(-) groups. Serosal invasion was observed in 19 of the 161 patients (12%). The 5-year recurrence-free survival rate was lower for S(+) (13.0%) than for S(-) (28.7%, P = 0.006). The 5-year overall survival (OS) rate was lower for S(+) (24.7%) than for S(-) (63.9%, P < 0.001). Regarding OS, serosal invasion, preoperative α-fetoprotein value, presence of invasion to hepatic veins, and liver cirrhosis were independent predictors in multivariate analyses. The 3-year OS rate after recurrence was poorer in the S(+) group (22.9%) than in the S(-) group (49.7%, P = 0.001). Serosal invasion was a strong predictor of worse outcomes after hepatectomy for HCC. Patients showing serosal invasion need close postoperative follow-up or consideration of adjuvant treatment.

Abstract OT1-01-05: A phase II study using talimogene laherparepvec as a single agent for inflammatory breast cancer or non-inflammatory breast cancer patients with inoperable local recurrence

Abstract Objective: The primary purpose of the study is to determine the local and systemic antitumor efficacy of talimogene laherparepvec in locally recurrent breast cancer patients with or without distant metastases, as evidenced by improved overall response rates. This will be the first study to use biopsy of distant disease to demonstrate whether systemic immune modulation has antitumor efficacy in breast cancer patients. BACKGROUND: Patients with locally recurrent breast disease frequently undergo multimodal treatment at the first occurrence of breast cancer, and because local treatment modalities such as surgical intervention and radiation are difficult to add, they subsequently receive systemic therapy. Talimogene laherparepvec (T-VEC) was developed to eliminate solid tumors and has since been considered as a potential treatment option for body surface tumors. In addition to T-VECinjected area, this agent is capable of modifying the immune response with the potential of inhibiting distant metastases. Hence, locally recurrent breast disease could benefit from T-VECregardless of concomitant distant metastases, and may offer a new local treatment option. Study Design and Treatment Plan: This is a single agent phase II study. Patients with breast cancer who have recurrence of chest wall disease with or without distant metastasis, have at least 1 injectable lesion ≥5 mm in longest diameter or multiple injectable lesions that in aggregate have a longest diameter of ≥ 5 mm, and meet inclusion and exclusion criteria will be eligible to participate in the study. Patient will receive T-VEC via intra-tumoral injection every 2 weeks after the first initial injection (3 weeks). STATISTICAL METHODS: Up to 35 patients will be enrolled in the study. The trial will be conducted using a two-stage design and the overall response rate will be estimated accordingly. It is assumed that the talimogene laherparepvec single agent will have a response rate of 20%. A response rate of 5% or lower will be considered treatment failure and the regimen will be rejected under this circumstance. Status of the study: Activation Date: Aug 2016. 6 patients have been treated. Enrollment continues. Sponsor: Amgen State of Texas appropriation for rare and aggressive breast cancer research. Citation Format: Willey JS, Marx AN, Lim B, Ibrahim NK, Valero V, Mittendorf EA, Reuben JM, Le-Petross HT, Whitman GJ, Krishnamurthy S, Woodward WA, Lucci A, Liu DD, Shen Y, Ueno NT. A phase II study using talimogene laherparepvec as a single agent for inflammatory breast cancer or non-inflammatory breast cancer patients with inoperable local recurrence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-01-05.

Patterns of local recurrence after radical cystectomy in a contemporary series of patients with muscle-invasive bladder cancer

To describe the epidemiology, clinical features, and prognostic factors of local recurrence (LR) in a large case series of patients treated by radical cystectomy (RC) for bladder cancer. A retrospective study was conducted on 903 patients treated in a single tertiary reference center. All cases of LR were identified. Descriptive analysis was performed on the clinical features, evolution, and overall mortality of these patients. Prognostic factors of LR were assessed using the Mann-Whitney test for continuous variables and the χ(2) test for categorical variables. Fifty-three patients were diagnosed with LR during follow-up (5.9 %). One patient had concomitant distant metastasis. Pain was the most frequent symptom leading to diagnosis. Mean time interval from RC to LR was 14.4 ± 13 months (1-64) with 50 % of cases diagnosed in the first postoperative year. Overall median survival of patients diagnosed with LR was 9 months [95 % confidence interval (6-11)]. Advanced pathological stage (T3 or T4) and lymph-node invasion were associated with increased LR rate in univariate and multivariate analysis. Presence of squamous cell carcinoma (SCC) was associated with a poorer prognosis after LR compared to pure urothelial carcinoma (p = 0.04). None of the parameters tested was associated with time interval between RC and LR diagnosis. LR is not uncommon, favored by high pathological stage (T3/T4), and has a very bad prognosis, particularly when SCC is present. LR must be carefully tracked during follow-up after RC, and optimal management of these cases remains to be determined.

The prognostic utility of LDH and CRP for survival after melanoma metastasectomy in the urogenital tract.

e19021 Background: Recent studies suggest that serum lactate dehydrogenase (LDH) and serum C-reactive protein (CRP) are risk factors for survival in patients with metastatic melanoma. However, due to the relatively low tropism of metastatic melanoma lesions in the urogenital tract the clinical benefit of metastasectomy in this highly selective group of patients remains uncertain. The objective of this study was to address the role of LDH and CRP as preoperative serological risk factors for survival in patients with solitary or concomitant metastatic melanoma lesions in the urogenital tract. Methods: All patients who were referred for metastasectomy in the urogenital tract in a tertiary center within 1999-2008 were considered for this analysis. Demographic, disease and survival data were collected. Elevated LDH activity was defined as &gt;250U/l and elevated serum CRP&gt;0.5mg/dl. The primary endpoint was overall survival (OS), calculated using Kaplan-Meier method with log-rank test and multivariate Cox-regression analysis. Results: Of a total of 21 patients,16 (76%) had solitary urogenital metastases and 5 patients (24%) concomittant non-urogenital metastases.Median OS after metastasectomy was 23 months (range: 3-59 months). LDH&gt;250U/l was significantly associated with decreased OS (27.6 vs. 6.0 months; p=0.001), but elevated CRP did not (24.1 vs. 20.7 months; p=0.93). No further significant differences in survival were found for age (p=0.76), gender (p=0.83), number of urogenital metastatic sites (0.97) and preoperative solitary vs. concomitant distant metastases (p=0.48). In multivariate analysis, adjusted for the TNM-stage grouping (M1a-c) and CRP level, elevated LDH maintained significance as negative prognostic factor for overall survival (p=0.0015). Conclusions: To our knowledge, this is the first study addressing the prognostic role of LDH and CRP in patients with melanoma urogenital metastases. If confirmed in large prospective studies, LDH level may be used for preoperative risk stratification in patients scheduled for melanoma metastasectomy in the urogenital tract to identify those patients who profit most from the surgical approach.

Surgery in metastatic breast cancer: Patients with a favorable profile seem to have the most benefit from surgery

Introduction About 3–10% of breast cancer patients have distant metastases (Stage IV) at initial presentation; standard treatment (in the Netherlands) of these patients consists of palliative systemic therapy. However, retrospective studies have shown an improved survival in patients who received surgery for their primary tumor. The aim of this study was to assess characteristics associated with surgical treatment and to determine the impact on survival in women with stage IV breast cancer. Methods A cohort of women with a diagnosis of breast cancer and concomitant distant metastases was retrospectively studied. Patient characteristics, treatment and survival distilled from medical files were evaluated using univariate and multivariable analysis. Results Of 171 patients included in this analysis, 59 underwent surgery. In multivariable analysis lower age, no medication use, lower clinical T-stage and lower grade were associated with receiving surgery. In 21 of the 59 patients (35%) who received surgery it was unknown at the time of surgery that the patient had metastatic disease. Stratified survival analyses showed an association between surgery and improved survival for young patients (HR 0.3; p = 0.02), without comorbidity (HR 0.4; p = 0.002), with no medication use (HR 0.5; p = 0.009), with a small tumor (HR 0.4; p = 0.01), no regional lymph node involvement (HR 0.4; p = 0.01), with positive Estrogen (HR 0.6; p = 0.02) or Progesterone receptor (HR 0.4; p = 0.03) and with only visceral metastases (HR 0.5; p = 0.03). In multivariable analyses, younger patients and patients without comorbidity that received surgery had an increased survival (HR 0.3; p = 0.03 and HR 0.5; p = 0.03, respectively). Conclusion This study showed that patients with the most favorable profile receive local surgery and that a survival gain for operated patients was seen in young patients and in patients without comorbidity.

Clinical Outcomes and Recurrence Predictors of Lymph Node Positive Urothelial Cancer After Cystectomy

Lymph node metastasis in patients who undergo radical cystectomy for bladder transitional cell carcinoma is considered a poor prognostic factor. However, patients with minimal lymph node involvement likely have a better outcome than those with extensive disease. We examined outcomes in patients with low volume lymph node metastasis and identified variables associated with disease recurrence. Our institution maintains a database of 1,600 patients with bladder transitional carcinoma who underwent radical cystectomy from 1971 to 2005 with intent to cure. All patients with low volume lymph node metastasis, defined as 1 or 2 positive lymph nodes, without concomitant distant metastasis were included in study. A total of 181 patients were identified. Median followup was 12.8 years, during which 96 patients experienced recurrence. Estimated 5 and 10-year recurrence-free survival was 43.8% and 40.9%, respectively. Multivariate analysis indicated that pathological stage/subgroup (RR 1.733, p = 0.015), lymph node density (RR 1.935, p = 0.014) and adjuvant chemotherapy (RR 0.538, p = 0.004) were significant independent predictors of recurrence-free survival. A considerable proportion of patients with low volume lymph node metastasis in our cohort remained free of recurrence during followup. Extravesical tumor extension and lymph node density greater than 4% were associated with a higher recurrence risk and adjuvant chemotherapy was associated with a lower risk. Although some patients with low volume lymph node metastasis may be cured by surgery alone, these data support adjuvant chemotherapy in these patients.

Presentation, location, and overall survival of pelvic recurrence after radical cystectomy for transitional cell carcinoma of the bladder: Dhar NB, Jones JS, Reuther AM, Dreicer R, Campbell SC, Sanii K, Klein EA, Section of Urologic Oncology, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH.

To evaluate the presentation, location, and overall survival of pelvic recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder. We reviewed a consecutive series of 130 patients who had a limited bilateral pelvic lymph node dissection (PLND) and RC between 1987 and 2000, and who later developed pelvic recurrence. All patients were staged N0M0 before RC and no patient received neoadjuvant radio/chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and the bifurcation of iliac vessels to the circumflex iliac vein. Pelvic recurrence was defined as a radiographic soft-tissue density of ≥2 cm below the bifurcation of the aorta. Kaplan-Meier and Cox proportional hazards analyses were used to determine if imaging or symptomatic presentation, age, pT stage, and pN status were predictive of overall survival. The median (range) time from RC to pelvic recurrence was 7.3 (1.2–55.4) months. No patients had concomitant distant metastasis. Of the patients, 61.5% were diagnosed with pelvic recurrence because of symptoms, and 38.5% by surveillance computed tomography (CT). Of the 130 patients, 128 died, with a median survival from the time of pelvic recurrence of 4.9 (0.1–129.3) months. The median overall survival time for pelvic recurrence diagnosed with CT was 21.6 months, vs. 10.6 months for symptomatic presentations ( P < 0.001). In the uni- and multivariate models, type of presentation (CT vs. symptomatic) and pT stage were predictors of overall survival, while age and pN status were not. The prognosis of patients with pelvic recurrence after RC for TCC is poor even with subsequent therapy, emphasizing the need for optimum local control at the time of initial treatment.

Presentation, location and overall survival of pelvic recurrence after radical cystectomy for transitional cell carcinoma of the bladder

To evaluate the presentation, location and overall survival of pelvic recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder. We reviewed a consecutive series of 130 patients who had a limited bilateral pelvic lymph node dissection (PLND) and RC between 1987 and 2000, and who later developed pelvic recurrence. All patients were staged N0M0 before RC and no patient received neoadjuvant radio/chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and the bifurcation of iliac vessels to the circumflex iliac vein. Pelvic recurrence was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Kaplan-Meier and Cox proportional hazards analyses were used to determine if imaging or symptomatic presentation, age, pT stage, and pN status were predictive of overall survival. The median (range) time from RC to pelvic recurrence was 7.3 (1.2-55.4) months. No patients had concomitant distant metastasis. Of the patients, 61.5% were diagnosed with pelvic recurrence because of symptoms, and 38.5% by surveillance computed tomography (CT). Of the 130 patients, 128 died, with a median survival from the time of pelvic recurrence of 4.9 (0.1-129.3) months. The median overall survival time for pelvic recurrence diagnosed with CT was 21.6 months, vs 10.6 months for symptomatic presentations (P < 0.001). In the uni- and multivariate models, type of presentation (CT vs symptomatic) and pT stage were predictors of overall survival, while age and pN status were not. The prognosis of patients with pelvic recurrence after RC for TCC is poor even with subsequent therapy, emphasizing the need for optimum local control at the time of initial treatment.

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas

Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas.Patients and methods: Thirty-nine patients were enrolled onto a phase I–II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy.Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1–7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia ≥grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred.Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patients.

Goblet cell carcinoid of the appendix

BackgroundGoblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management.MethodsPublished studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix.ResultsBased on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation.ConclusionGCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination.

The role of surgical management of locally recurrent rectal cancer(LRRC)

3712 Background: Use of salvage surgery in the treatment of recurrent rectal cancer is controversial because of the poor overall survival and the morbidity relevant to extirpative surgery in such patients. Methods: Twenty nine patients treated by surgery with curative intent for LRRC from 1998 to 2004 were analyzed. Postopearative morbidity, mortality and prognosis were analyzed. Median follow up time after salvage surgery was 33.2months (range, 1 to 80.8months). Results: Patient backgrounds: Surgery for primary tumor; abdominoperineal resection(APR) 16cases/Low anterior resection 13cases, Dukes stage; A 1/B 16/C 10/unknown 2, Adjuvant therapy after primary surgery; none 5/systemic chemotherapy 17/unknown 7, The surgical management of recurrent tumor included 3 APR, 4 abdominosacral resection, 13 total or posterior pelvic exenteration with/without sacral resection, and 9 local tumor excision. Curative operation (R0) was performed in 23 patients. Median operative time was 885 minutes (range, 130 to 1500 min.). Median estimated blood loss was 5550 ml (range, 310 to 60600 ml.). Postoperative mortality is 1/29(3.4%). Nineteen patients suffered perioperative complications. The morbidity included perineal wound infection (n=8, 27%), pelvic cavity infection (n=6, 21%), bowel obstruction (n=3, 14%), urinary tract disorder (infection, stenosis of ureter, dysfunction) (n=10, 34%), perioperative hemorrhage (n=2, 6.9%). The median overall survival after local recurrence was 20.1 months. Survival rate in patients with concomitant distant metastasis (n=5) after 1 and 3 years is 100% and 37.5%, respectively, and survival rate without concomitant distant metastasis (n=24) is 95.5% and 56.6% respectively. Conclusions: Surgical management of LRRC can be performed safely with low mortality, but still carries a significant morbidity. Our results are in agreement with other international literature data and further follow up is needed to justify this treatment. No significant financial relationships to disclose.

Prognostic index for extremity soft tissue sarcomas with isolated local recurrence.

Local recurrence occurs in 10% to 20% of patients with extremity soft tissue sarcomas despite optimal treatment. The association of local recurrence with subsequent survival is controversial and conflicting. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy. Data collected from 110 patients with locally recurrent extremity soft tissue sarcomas were studied. The influence of clinical and pathologic factors on local recurrence, distant metastasis, and disease-specific survival were analyzed by univariate and multivariate techniques. Of the 110 patients who presented with local recurrence, 92 had an isolated local recurrence and 18 had prior or concomitant distant metastases. The 5-year disease-specific survival for all patients was 63% and for those with isolated local recurrence, it was 69%. Histologic grade, malignant fibrous histiocytoma histology, pathologic margins, previous local recurrence, and prior radiotherapy were independent prognostic factors for subsequent local recurrence. Tumor size, histologic grade, and time to local recurrence were independent prognostic factors for distant metastasis and disease-specific survival. A prognostic index was calculated by assigning a score of 1 to 3 for each of the three independent prognostic factors for survival and added to give the prognostic index for each patient. As the prognostic index increased from 3 to 9, there was a progressive increase in the hazard ratios and a corresponding deterioration in survival. The patients were then categorized into three prognostic groups based on the hazard ratios for disease specific survival. The differences in the survival curves were highly statistically significant (P < .0001). Tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.

Results of chest wall reirradiation using pulsed-dose-rate (PDR) brachytherapy molds for breast cancer local recurrences

Purpose: We report in a retrospective study on the effect and toxicity of chest wall reirradiation using pulsed-dose-rate (PDR) afterloading molds. Methods and Materials: Between 1993 and 1999, a total of 58 patients were treated. All patients presented with locally recurrent breast cancer (31 patients had concomitant distant metastases) after mastectomy and a previously completed course of radiation therapy (median, 54 Gy; range, 36–70). Indication for reirradiation was a progressive macroscopic skin recurrence in 30 cases and an incomplete surgical resection in 28 patients. Standard treatment consisted of a split course with two fractions of 20 Gy (interval, 31 days). The reference dose was prescribed to the skin surface at 5 mm distance from the source. PDR brachytherapy (37 GBq, 192Ir) was carried out after geometric distance optimization with 0.5–1 Gy/pulse/h. The irradiated median area was 423 cm 2 (range, 100–919). The median follow-up was 18 months (range, 7–84). Results: The actuarial 1-, 2- and 3-year local recurrence-free survival rates in patients treated for macroscopic disease (microscopic disease in parenthesis) were 89% (96%), 81% (85%), and 75% (71%). Local control was obtained in 24/30 (22/28) patients. Twenty-nine of the 34 patients (85%) who deceased during follow-up were locally controlled. 9/58 patients experienced Grade III acute toxicity, 35/58 patients Grade III (29/58 telangiectasia, 6/58 contracture), and 4/58 Grade IV late toxicity (RTOG/EORTC). Conclusion: Reirradiation of the chest wall using PDR brachytherapy molds is effective and provides a high local control rate with acceptable toxicity.

ILEAL NEOBLADDER AND LOCAL RECURRENCE OF BLADDER CANCER: PATTERNS OF FAILURE AND IMPACT ON FUNCTION IN MEN

Creation of an ileal neobladder has become a standard procedure in patients undergoing cystectomy for invasive bladder cancer. We evaluated the impact of local recurrence on ileal neobladder function and survival. Between April 1986 and February 1997, 357 men underwent radical cystectomy and ileal neobladder substitution at our institution. We retrospectively reviewed the records of these patients to determine patterns of local recurrence and survival rates. Local recurrence developed in 43 of the 357 patients (12%), in whom median survival plus or minus standard deviation was 17 +/- 1.6 months and median time to recurrence was 10 months (range 2 to 41). Of the 43 patients with local recurrence at followup 36 had local advanced cancer on the final pathological evaluation (stage pT3a or node positive, or greater). A total of 17 patients (43%) had concomitant distant metastasis. Of the 43 patients 3 are alive at 36, 48 and 147 months, respectively. Death was due to disease in 36 cases, chemotherapy related complications in 3 and another cause in 1. Of the 43 patients 40 maintained good neobladder function. Local recurrence interfered with the upper urinary tract in 24 cases, neobladder in 10 and intestinal tract in 7. The neobladder was removed only in 1 patient due to a neovesical intestinal fistula. The local recurrence rate after orthotopic urinary reconstruction is 12%. Survival after local recurrence is diagnosed is limited despite multimodality therapy. However, most patients may anticipate normal neobladder function even in the presence of recurrent disease or until death. Thus, creating orthotopic diversion after cystectomy in patients with locally advanced bladder cancer, including macroscopically or microscopically positive lymph nodes, is safe.

Locoregional recurrence of adenocarcinomas of the rectum treated with irradiation combined with or without excision surgery

Retrospective study to analyze the results of external beam radiation treatment with or without surgery for loco-regional recurrence of adenocarcinoma of the rectum following previous surgery without pre- or post-operative radiotherapy. Between March 1973 and November 1991, 211 patients with loco-regional recurrence of rectum cancer were treated with external beam radiation treatment. Radical surgery was the only initial treatment modality. Surgical resection of local recurrence was done in 36 patients and only 17 patients could undergo complete resection. Forty-seven patients underwent radiotherapy (RT) combined with surgery and 164 received external beam radiation treatment alone to a mean total dose of 46 Gy. Among the 151 patients whose recurrence was revealed by pain, 64 (42%) were considered to have a complete symptomatic response after loco-regional treatment with radiosurgery or RT alone. The mean duration of response was 12 months. The 3-year overall survival rate was 16%. Five prognostic factors decreased the overall survival rate in multivariate analysis: high age, sex (male), concomitant distant metastasis, no tumor resection, and low total radiation dose with external beam radiation treatment alone. The 3-year overall survival rate for patients with completely resected recurrences was 39%. External beam RT treatment can only be considered a palliative symptomatic treatment. New techniques of early detection of local recurrence and new combined modalities approaches (radiation sensitizers or intra-operative radiotherapy) with surgical resection in some favorable cases should be studied.

The Possible Prognostic Significance of p53 Immunostaining Status of the Primary Tumor in Patients Developing Local Recurrence after Breast-Conserving Surgery

Prognostic factors for distant metastases in patients with local recurrence after breast-conserving treatment (BCT) were studied. Fifty-six patients who developed local recurrence after BCT were recruited from 18 key hospitals/institutes in Japan. All 10 patients whose primary tumors were DCIS fared well without evidence of distant failure for a median follow-up period of 57 months (range 41–72) after the local recurrence. Inflammatory local recurrence was observed in 5 patients whose prognosis was grave: 3 with concomitant distant metastases and 1 developing them 7 months later. In the remaining 41 patients with noninflammatory local recurrence, various clinicopathological factors including age, disease-free interval, histology of the primary and recurrent tumors, axillary lymph node status, estrogen and progesterone receptor, immunohistochemical staining of erbB2 and p53 protein were evaluated as prognostic factors. Only the p53 immunostaining status of the primary tumor was found to be a significant prognostic indicator for distant metastases; distant disease-free survival at 5 years after the local recurrence was 92% for patients with p53-negative cancers and 51% for those with p53-positive cancers (p < 0.05).

Nephron Sparing Surgery in Patients with Metastatic Renal Cell Carcinoma

Purpose We evaluated the role of nephron sparing surgery in patients with metastatic renal cell carcinoma. Materials and Methods A total of 15 patients with metastatic renal cell carcinoma underwent nephron sparing surgery and treatment of metastases, including 4 who received adjunctive biological response modifier therapy. The 9 patients in group 1, who previously underwent contralateral nephrectomy for renal cell carcinoma and complete resection of all metastases, presented for treatment of localized renal cell carcinoma in the remaining kidney with no other evidence of disease. The 6 patients in group 2 presented with localized renal cell carcinoma requiring nephron sparing surgery and concomitant distant metastases. Mean postoperative followup was 30.4 months. Results Of 9 patients in group 1, 6 (66.7 percent) were disease-free at a mean of 31.3 months after nephron sparing surgery and 102.2 months after detection of metastatic disease, while 3 (33.3 percent) died at a mean of 53.3 and 73.0 months, respectively. Among the 6 patients in group 2, 4 (66.7 percent) were disease-free at a mean followup of 16.8 months and 2 (33.3 percent) died at a mean of 20.5 months postoperatively. Of the 4 patients who received adjunctive biological response modifier therapy 3 were disease-free at a mean of 12.7 months and 1 died 7 months after treatment. Satisfactory overall renal function was preserved in 14 of 15 patients after nephron sparing surgery. Conclusions We conclude that nephron sparing surgery can provide effective treatment for select patients with renal cell carcinoma and previously or recently treated metastatic disease.

Multivariate analysis of risk factors influencing survival in 110 ethnic Chinese with papillary thyroid cancer.

Data from 110 Chinese patients presenting with papillary thyroid cancer to a single institution up to December 1985 have been analyzed to evaluate the possible risk factors affecting survival. There were 83 women and 27 men with an age range of 15 to 78 years (mean 45 years, median 42 years). The longest follow-up period is 39 years and the median 10 years. Cervical lymph node recurrence more than 6 months after surgery developed in 12 patients, of whom 1 died with a concomitant distant metastasis. "Thyroid bed" tumor recurrence, after apparently complete surgery, presented in 10 patients and resulted in 5 deaths. Distant metastases were identified in 17 patients with 7 deaths. Another 4 patients died from advanced local disease incompletely resectable on presentation. The following seven risk factors for survival were selected for multivariate analysis: age, sex, tumor size, histologic evidence of extrathyroidal spread, lymph node recurrence, neck recurrence, and distant metastases. Age, size, neck recurrence, and distant metastases were all significant on univariate analysis. Using Cox proportional hazards regression in the multivariate analysis of these seven factors, only age (p < 0.0001) was shown to be significant. Age over 40 years on first diagnosis was a highly significant indicator of high risk (p = 0.0003, log-rank).