Multifactorial analysis of survival in primary extremity liposarcoma

The treatment of extremity soft tissue sarcoma is now directed at limb preservation with the addition of various adjuvant therapies to improve treatment results. To achieve this goal, a knowledge of prognostic factors for extremity soft tissue sarcoma becomes increasingly critical. The object of this study was to analyze prognostic factors for survival in patients with extremity liposarcoma.Eighty-three patients with primary localized extremity liposarcoma, admitted from 1968 to 1978, were retrospectively reviewed. Surgical resection was the primary mode of treatment. Eleven prognostic factors were analyzed. Tumor factors included: histologic subtype, tumor grade, size, depth, invasion of vital structures, and site; operative factors included: type of operation, and surgical margins; and patient factors included: symptoms, age at diagnosis, and sex. Kaplan-Meier survival curves, and univariate and stratified log-rank tests of association were performed. Independent factors for predicting survival were identified using the Cox model stepwise regression technique.In univariate analysis of the entire group of patients, 5 factors were significant for tumor mortality: tumor grade (p=0.00005), histologie subtype (p=0.00025), tumor size s5 cm (p=0.005), type of surgery/ margin (p=0.0001), and invasion of vital structures (p=0.008). When associations among all factors were analyzed, it was found that many factors were interdependent. The independent prognosticators were, therefore, determined according to the Cox model technique. For the multivariate analysis, well-differentiated and lipoblastic liposarcomas were excluded because of lack of survival variation within each group. The former group had no tumor-related deaths and the latter group showed 80% tumor mortality. The remaining patients with myxoid, high-grade fibroblastic and pleomorphic liposarcoma were subjected to multivariate analysis. Three factors emerged as independent prognostic predictors: high-grade tumor (p=0.013), inadequate resection/amputation (p=0.003), and tumorcm (p=0.04).

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Resumen El tratamiento del sarcoma de tejidos blandos de las extremidades actualmente está orientado hacía la preservación del miembro con la adición de diversas modalidades terapéuticas adyuvantes para mejorar los resultados. Para lograr este propósito, se hace recientemente importante disponer de conocimientos relativos a los factores de pronóstico en los sarcomas de tejidos blandos. El propósito del presente estudio fue analizar factores de pronóstico de supervivencia en pacientes con liposarcoma de las extremidades.Ochenta y tres pacientes con liposarcoma de localización primaria en la extremidad, hospitalizados entre 1968 y 1978, fueron revisados en forma retrospectiva. La resección quirúrgica fue la modalidad primaria de tratamiento. Once factores de pronóstico fueron analizados. Los factores tumorales incluyeron: subtipo histológico, grado tumoral, tamaño, profundidad, invasión de estructuras vitales, y ubicación; los factores operatorios fueron: tipo de operación, y márgenes quirúrgicos; y los factores relativos al paciente fueron: síntomas, edad en el momento del diagnóstico, y sexo. Se realizaron curvas de sobrevida de Kaplan-Meier, y pruebas univariables y de asociación estratificada. Los factores independientes para predecir sobrevida fueron identificados mediante la técnica regresiva del modelo de Cox.En el análisis univariable del grupo total de pacientes, 5 factores aparecieron de significación en cuanto a mortalidad tumoral: grado tumoral (p=0.00005), subtipo histológico (p= 0.00025), tamaño tumoral5 cm (p=0.005), tipo de cirugía/ márgen (p=0.0001), invasion de estructuras vitales (p= 0.008). Al analizar las asociaciones entre todos los factores se encontró que muchos factores son interdependientes. Los pronosticadores independientes fueron determinados entonces de acuerdo a la técnica del modelo de Cox. Para el análisis multivariable, bien diferenciado, y los liposarcomas lipoblásticos fueron excluídos debido a que no hubo variación en la sobrevida entre cada grupo. El primer grupo no exhibió muertes relacionadas con el tumor y el último mostró una mortalidad de causa tumoral de 80%. Los pacientes restantes con liposarcomas mixoides, y liposarcomas de alto grado fibroblásticos y pleomórficos fueron sometidos a análisis multivariable. Tres factores emergieron como predictores independientes de pronóstico: tumores de alto grado (p=0.013), resección/amputación inadecuada (p=0.003), y tumor5 cm (p=0.04).

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Résumé Grâce à l'apport des traitements adjuvants qui améliorent les résultats, l'attitude thérapeutique dans les sarcomes des parties molles s'oriente actuellement vers la conservation du membre. Il est donc indispensable de disposer de facteurs pronostiques des sarcomes des parties molles. Le but de cette étude était d'analyser les facteurs pronostiques de survie chez des patients ayant un liposarcome des extrémités.Les dossiers de 83 patients ayant un liposarcome primitif des extrémités et admis dans notre service entre 1968 et 1978, ont été revus rétrospectivement. La résection chirurgicale a été pratiquée en premier. Onze facteurs ont été pris en considération: facteurs tumoraux: type histologique, degré de malignité, taille de la tumeur, profondeur d'invasion, invasion des structures vitales, et site; facteurs opératoires: type d'opération, et largeur des marges de sécurité; facteurs propres au malade: symptômes, âge au moment du diagnostic, et sexe. Les méthodes statistiques employées comprenaient les courbes de Kaplan-Meier, le logrank et l'analyse monofactorielle. Les facteurs permettant de prévoir la survie ont été identifiés selon le modèle regressionnel pas-à-pas de Cox.De l'analyse monofactorielle de tous les patients, il ressort que 5 facteurs étaient significatifs: le degré de différenciation (p=0.00005), le type histologique (p=0.00025), la taille de la tumeur5 cm (p=0.005), le type de chirurgie et la marge de sécurité (p=0.0001), et l'invasion des structures vitales (p=0.008). Plusieurs facteurs d'entre eux étaient indépendants. Ils ont été analysés selon le modèle de Cox. A l'analyse multifactorielle, les liposarcomes bien différenciés et de type blastique ont été exclus en raison de l'absence de différence de survie entre les groupes. Dans le premier, il n'y avait pas de mort en rapport avec la tumeur et, dans le deuxième groupe, la mortalité était de 80%. Les autres patients avaient une tumeur myxoïde, fibroblastique de haut degré de malignité et pléomorphologique et ont eu une analyse multifactorielle. Les 3 facteurs pronostiques indépendants étaient: le degré de malignité (p=0.013), l'insuffisance de la résection (p=0.003), et la taille de la tumeur 5 cm (p=0.04).

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Presented at the Société Internationale de Chirurgie in Toronto, Ontario, Canada, September, 1989.     

Effect of perioperative blood transfusion on recurrence and survival in 232 primary high-grade extremity sarcoma patients

Background: Allogeneic blood transfusion (BT) has been implicated as an unfavorable factor influencing cancer recurrence and overall survival. Methods: To investigate this, 232 consecutive localized, high-grade extremity soft tissue sarcoma (STS) patients admitted between January 1, 1983, and December 31, 1989, were analyzed from our prospective database by univariable and Cox multivariable statistical methods. Results: Twenty-eight patients developed a local recurrence (LR). Factors found significantly unfavorable for the rate of developing an LR by uni- and multivariable tests were age >60 years and positive microscopic margin. Eighty-nine patients developed a distant metastasis (DM) and 72 patients died of their tumor. Median follow-up of survivors was 48 months. Unfavorable factors for DM and tumor mortality (TM) by univariable analysis included large size, deep tumor (that involved or was below the superficial fascia), positive microscopic margin, invasion of a vital structure, operative blood loss, duration of operation, and perioperative BT (whole blood or packed cells -24 to +48 h of curative operation). Multivariable analysis found large size, deep tumor, and positive margin significant independent unfavorable factors for DM and TM. The effect of BT was not a significant independent prognosticator for LR, DM, or TM by multivariable analysis (p=0.26, 0.56, 0.08, respectively), The only factor that was found to be significant in a multivariable analysis of factors contributing to postmetastasis survival was time <6 months until metastasis (p=0.008). BT had no significant impact on postmetastasis survival (p=0.42). There was a significant association between BT and deep, large tumors. As the size of deep tumors increased from <5, 5<10, 10<15, or15 cm, the amount transfused was 15, 16, 49, and 68% (p<0.00001). Also, BT was significantly (p<0.005) associated with low hematocrit at initial diagnosis, blood loss during surgery, and the length of the surgical procedure. Conclusions: These data emphasize the importance of size, depth, and margin on distant recurrence and death for localized high-grade extremity STS. In the absence of a randomized trial, the impact of allogeneic blood transfusion would appear to be due to its strong association with large size and deep tumor invasion. This study also highlights the importance of a multivariable analysis and long-term follow-up to better define this controversial question.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Analysis of potential risk factors in the survival of patients with primary retroperitoneal liposarcoma

IntroductionThe present work is an observational study of a series of variables regarding overall survival and disease-free survival in patients diagnosed with primary liposarcoma.MethodsThe study is prospective with retrolective data collection that includes all patients with primary liposarcoma referred to Hospital Son Espases University Hospital, Palma de Mallorca, Spain from January 1990 to December 2019.ResultsThe study includes 50 patients and the compartment surgery was performed in 18 patients (36%) of cases. The mean overall survival of the sample was 15.57 years (95% CI: 12.02–19.12) and the mean disease-free survival was 6.70 years (95% CI: 4.50–8.86).ConclusionCompartment surgery has not shown benefits in terms of overall survival and disease-free survival. The ASA classification (≥3) predicts a poor prognosis in both overall survival and disease-free survival. Resection with free margins, described on the pathological results and defined in this work as R0, show better disease-free survival.     

Subtype specific prognostic nomogram for patients with primary liposarcoma of the retroperitoneum, extremity, or trunk

OBJECTIVE: To determine the prognostic significance of histologic subtype in a large series of patients with primary liposarcoma (LS) and to construct a LS-specific postoperative nomogram for disease-specific survival (DSS). SUMMARY BACKGROUND DATA: Nomograms, used to define and predict outcome following operative intervention, may contain variables not conventionally used in standard staging systems. A 12-year DSS postoperative nomogram for all sarcomas has already been established. METHODS: From a single-institution prospective sarcoma database, patients with primary extremity, truncal, or retroperitoneal LS treated between 1982 and 2005 were identified. Histology was reviewed by a sarcoma pathologist and divided into 5 subtypes. A nomogram predictive of 5- and 12-year DSS was developed. RESULTS: Of 801 patients with primary LS resected with curative intent, 369 (46%) presented with well-differentiated, 143 (18%) dedifferentiated, 144 (18%) myxoid, 81 (10%) round cell, and 64 (8%) pleomorphic histology. The median tumor burden was 15 cm (range, 1-139 cm). At last follow-up, 560 patients were alive with a median follow-up time of 45 months (range, 1-264 months) and 51 months for surviving patients. The 5- and 12-year DSS rates were 83% (95% confidence interval [CI], 80%-86%) and 72% (95% CI, 67%-77%), respectively. The nomogram was drawn on the basis of a Cox regression model. The independent predictors of DSS were age, presentation status, histologic variant, primary site, tumor burden, and gross margin status. The nomogram was internally validated using bootstrapping and shown to have excellent calibration. The concordance index was 0.827 compared with 0.776 for the general sarcoma postoperative nomogram for 12-year DSS. CONCLUSION: The LS-specific nomogram based on histologic subtype provides more accurate survival predictions for patients with primary LS than the previously established generic sarcoma nomogram. DSS nomograms aid in more accurate counseling of patients, identification of patients appropriate for adjuvant therapy, and stratification of patients for clinical trials and molecular analysis.     

Histologic response of high-grade nonmetastatic osteosarcoma of the extremity to chemotherapy,

In 510 patients with osteosarcoma of the extremity treated at the authors' institute between March 1983 and June 1995 with different regimens of neoadjuvant chemotherapy, factors that influenced the histologic response were investigated. The rate of total necrosis was not related to the patients' gender, age, site, size of tumor, serum of alkaline phosphatase values, or route of cisplatin administration. The histologic response significantly and independently correlated with the number of drugs administered before surgery and with the histologic subtype of the tumor. According to the number of drugs used, the percentage of total necrosis was 31% for a four-drug regimen, 18% for a three-drug regimen, and only 1.5% for a two-drug regimen. According to the histologic type, the rates of total necrosis were 41% for telangiectatic tumors, 36% for fibroblastic tumors, 15% for osteoblastic tumors, and 3% for chondroblastic tumors. The authors concluded that in neoadjuvant therapy of osteosarcoma, the histologic response to preoperative treatment, which correlates with prognosis, depends on the effectiveness of the chemotherapy regimen and on some features intrinsically inherent to the tumor. These data should be considered when selecting the type of treatment (adjuvant or neoadjuvant) and the combinations of drugs to be used in preoperative treatment of patients with osteosarcoma.     

The impact of primary stage on survival in patients with lymph node positive bladder cancer

PURPOSE: Contemporary series indicate that survival of cystectomy candidates with node positive bladder cancer is favorable when the primary tumor is confined to the bladder wall and lymph node involvement is minimal. However, these series lack node negative controls with a similar tumor stage to determine accurately the true impact of pelvic lymphadenectomy and radical cystectomy on survival. MATERIALS AND METHODS: We retrospectively analyzed disease specific survival in 686 consecutive cystectomy candidates of whom 193 (28.1%) had node positive disease at radical cystectomy. To correct for bias towards higher P category in the node positive group we subdivided groups into organ and nonorgan confined categories to compare outcome between node negative and node positive cases. RESULTS: The frequency of organ confined disease in node positive cases was 22.8% compared to 59.2% in node negative cases. Although when analyzing the entire group disease specific survival was significantly decreased in node positive cases, after correction for P stage we found no statistically significant differences in survival between N0 and N1 cases in the organ confined group (p = 0.4267). Differences between N0 and N1 cases in nonorgan confined disease were statistically significant (p = 0.0276). Significance levels were more pronounced when cases with N2 or N3 categories were compared with node negative cases. Comparison of survival between node negative and N2 or N3 in either group revealed significant differences indicating limited impact of surgery alone at this disease stage. CONCLUSIONS: Patients with N1 disease seem to benefit from pelvic lymphadenectomy and radical cystectomy as evidenced by similar outcome in those with node negative disease and similar P stage of the primary tumor. However, the observed benefit rapidly disappears when more than 1 lymph node is involved and additional therapy other than surgery seems appropriate.     

Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity

BACKGROUND: We reviewed single-institution experience using brachytherapy alone for primary high-grade soft tissue sarcoma of the extremity. METHODS: Between July 1982 and September 1997, 202 adult patients with primary high-grade soft tissue sarcoma of the extremity were treated with limb-sparing surgery and adjuvant brachytherapy. All patients underwent complete gross resection, but the margin of resection was microscopically positive in 18% of patients. The median dose of brachytherapy was 45 Gy delivered over 5 days. Tumors located in the shoulder or groin were defined as central location. Complications were assessed in terms of wound complications, bone fracture, and peripheral nerve damage. RESULTS: With a median follow-up of 61 months, the 5-year local control, distant relapse-free survival, and overall survival rates were 84%, 63%, and 70%, respectively. On multivariate analysis, poor local control correlated with shoulder location, positive microscopic margins of resection, and nonshoulder upper extremity site. The 5-year actuarial rates of wound complications requiring reoperation, bone fracture, and grade > or = 3 nerve damage were 12%, 3%, and 5%, respectively. CONCLUSIONS: Adjuvant brachytherapy provides adequate local control and acceptable morbidity that compares favorably with data reported for external beam radiation. Shoulder tumor location was identified as an independent prognostic factor for poor local control, mandating further improvement in the local management of these tumors.     

Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma

PURPOSE: To determine if ifosfamide-based chemotherapy (IF) offers a survival benefit to adult patients with primary extremity synovial sarcoma. PATIENTS AND METHODS: Prospectively collected patient data from 2 institutions was used to identify all adult patients (>or=16 years) with >or=5 cm, deep, primary, extremity, synovial sarcoma that underwent surgical treatment of cure from 1990 to 2002. A total of 101 patients were identified and the median follow-up for survivors was 58 months. Clinical, pathologic, and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS), and local recurrence-free survival (LRFS). RESULTS: Sixty-eight (67%) patients were treated with IF and 33 (33%) patients received no chemotherapy (NoC) for the primary tumor. The characteristics of the IF-treated patients [median tumor size = 7.2 cm; monophasic n = 46 (68%)] were similar to NoC patients [median tumor size = 7 cm; monophasic n = 23 (70%)]. The 4-year DSS of the IF-treated patients was 88% compared with 67% for the NoC patients (P = 0.01). Smaller size (HR = 0.3 per 5-cm decrease, P < 0.0001) and treatment with IF (HR = 0.3 compared with NoC, P = 0.007) were independently associated with an improved DSS. Treatment with IF was independently associated with an improved DRFS (HR = 0.4, P = 0.03) but not associated with an improved LRFS (P = 0.39). CONCLUSION: Ifosfamide-based chemotherapy was associated with an improved DSS in adult patients with high-risk, primary, extremity, synovial sarcoma and should be considered in the treatment of such patients.     

Long term survival in non-encapsulated primary liposarcoma of the mediastinum.

An elderly woman presented with dyspnoea secondary to extensive mediastinal invasion by a primary well differentiated liposarcoma of the mediastinum. Five years after partial resection and postoperative radiotherapy (45 Gy) she is alive and well. To our knowledge, long term survival has not previously been reported for a non-encapsulated mediastinal liposarcoma treated by incomplete resection and subsequent radiation therapy.     

肝外恶性肿瘤对合并肝癌的多原发癌患者生存影响的Meta分析

目的：评价肝外恶性肿瘤对合并肝癌的多原发癌患者生存率的影响。方法系统回顾公开发表的比较合并肝癌的多原发癌患者和单患肝癌患者生存率且随访严密的临床研究,评估原始研究的质量,对符合条件的研究结果进行Meta分析,计算多原发癌相对单患肝癌死亡危险的优势比（OR）,评价肝外恶性肿瘤对患者生存期的影响。结果共6篇文献符合入选标准,总样本量2431例。包括肝癌合并多原发癌病例207例,死亡136例;单患肝癌组2224例,死亡1598例;合并OR=0.93,95％CI为0.67～1.28。结论肝外肿瘤既没增加也没降低死亡危险,合并肝癌的多原发癌并不意味预后更差,采取积极的治疗是患者获得长期生存的关键,相对于肝外肿瘤需要优先治疗肝癌。     

Sociodemographic disparities in chemotherapy treatment and impact on survival among patients with metastatic bladder cancer

Objective

To evaluate how socioeconomic status and other demographic factors are associated with the receipt of chemotherapy and subsequent survival in patients diagnosed with metastatic bladder cancer.

Prediction of survival in patients with high-grade soft tissue sarcoma

Summary Using the Cox proportional hazards model, and considering tumour necrosis and vascular invasion by tumour as additional factors in assessment, a series of 88 patients with primary Grade III and IV soft tissue sarcomas of the locomotor system was analysed for factors associated with death due to the tumour. Grade IV malignancy, a tumour size larger than 10 cm., tumour necrosis, and vascular invasion by tumour cells were significant risk factors. Patients with 0 or 1 risk factor, one half of the cases, had a 3 year survival rate of more than 90%, whereas the figure was 65% for those with 2 risk factors and 20% for those with 3 or 4 risk factors.

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Résumé Les auteurs ont utilisé le modèle d'erreurs proportionnelles de Cox et tenu compte, dans l'évaluation, de la nécrose tumorale et de l'envahissement vasculaire par la tumeur comme facteurs additionnels de risque. Une série de 88 malades atteints de sarcome primitif des parties molles de l'appareil locomoteur de degré III et IV a été analysée pour étudier les facteurs associés à la mort par tumeur. La malignité de degré IV, une tumeur de plus de 10 cm de large, la nécrose tumorale et l'invasion des vaisseaux par les cellules tumorales sont des facteurs de risque significatifs. Les malades présentant 0 ou 1 facteur de risque (la moitié des cas) ont un taux de survie à 3 ans de plus de 90% alors qu'il n'est que de 65% pour ceux qui présentent 2 facteurs de risque et 20% pour ceux qui en ont 3 ou 4.

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Supported by: John och Augusta Perssons Stiftelse; Stiftelsen för Bistand at Vanföra i Skane     

The impact of menstruation persistence or recovery after chemotherapy on survival in young patients with hormone receptor negative breast cancer

IntroductionHormone replacement therapy can diminish hormone depletion-related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Recovery of menstruation after chemotherapy-induced amenorrhea in young hormone receptor-negative BC patients however, is accepted. To determine the safety of this strategy, we investigated the effect of recovery of menstruation on disease-free survival (DFS) and overall survival (OS) in young hormone receptor-negative BC patients treated with (neo)adjuvant chemotherapy.MethodsWe selected 636 patients from a single-center cohort with early stage hormone receptor-negative BC and under the age of 50 years when treated with chemotherapy. Sufficient data on course of menstruation in medical records was retrospectively found for 397 patients, of whom 299 patients (75%) had a recovery of menstruation after chemotherapy. We used Cox proportional hazards models to estimate hazard ratios (HR) for the effect of recovery of menstruation on DFS and OS.ResultsPatients with recovery of menstruation after chemotherapy less frequently had lymph node involvement at diagnosis (45% vs 66%, p = 0.001). After a median follow-up of 6.7 years, the adjusted hazard ratios were 1.45 (95% CI: 0.83–2.54) for DFS and 1.19 (95% CI: 0.71–1.98) for OS.ConclusionNo significantly increased recurrence risk was found for hormone receptor-negative BC patients with recovery of menstruation after chemotherapy. However, the outcome of the multivariable model is not reassuring and a potentially increased recurrence risk cannot be excluded. The results need to be validated in a larger prospective study for a more definitive answer.     

Neoadjuvant chemotherapy followed by salvage surgery: effect on survival of patients with primary noncurative gastric cancer

The prognosis for gastric cancer patients who undergo noncurative resection is extremely poor. This study evaluated the effects of neoadjuvant chemotherapy for primary noncurative gastric cancer. Thirty-four patients with biopsy-proven noncurative gastric cancer were treated with either of two neoadjuvant chemotherapies: FEMTXP (5-fluorouracil, epirubicin, methotrexate, cisplatin) or THP-FLPM (pirarubicin, 5-fluorouracil, leucovorin, cisplatin, mitomycin C). Noncurability was determined by conventional staging procedures, staging laparoscopy, and exploratory laparotomy. After chemotherapy the resectability of the tumors was reassessed. Patients who were judged to be candidates for curative resection underwent salvage surgery. Of the final 33 patients, 8 (24.2%) showed a major response [0 complete response (CR), 8 partial response (PR)]. In three patients the second laparoscopy revealed disappearance of the peritoneal metastasis. Of the 33 patients, 14 (42.4%) underwent salvage surgery, including 8 curative resections (2 curability A, 6 curability B). Pathologic examinations revealed a grade 2 response in eight patients but no grade 3 response. Univariate analysis showed the following to be significant prognostic factors: histology type (differentiated type vs. undifferentiated type; p = 0.035), T4 as a noncurative factor (T4 vs. T3 or less; p = 0.025), clinical response (PR + no change vs. progressive disease; p = 0.002), and salvage surgery (resected vs. unresected; p = 0.001). Among these factors, salvage surgery was found to be the only independent prognostic factor by multivariate analysis, with a relative risk of 0.253 and a 95% confidence interval of 0.066 to 0.974. The treatment was well tolerated. Major toxicities of WHO grade 3 or more were leukopenia in 20 (60.6%), gastrointestinal toxicities in 5 (15.2%), renal toxicities in 2 (6.1%), and alopecia in 1 (3.0%). In conclusion, neoadjuvant chemotherapy is effective for primary noncurative gastric cancer when salvage surgery can be performed. A chemotherapy regimen with a higher complete response rate would improve the prognosis of this dismal disease even more.     

Advances in chemotherapy for patients with extremity soft tissue sarcoma

Doxorubicin-based chemotherapy does not appear to offer a survival benefit to patients who have high-risk primary extremity soft tissue sarcomas, whereas ifosfamide-based chemotherapy does. This benefit is likely histology- and size-specific. Until a less toxic targeted systemic therapy is developed, treatment with ifosfamide should be strongly considered in patients who have high-risk primary extremity soft tissue sarcomas.