Assessing prognosis for high-grade soft-tissue sarcomas: search for a marker

BACKGROUND: Although improved staging technology, limb-sparing surgery, and adjunctive radiation and chemotherapy have improved the outlook for patients with malignant soft-tissue tumors of the trunk and extremities, it is evident that we cannot predict which patients will develop distant metastases. Although local control is now frequently achieved, most series of high-grade soft-tissue sarcomas carry a mortality rate of > 50%. METHODS: In a retrospective study of 93 patients with high-grade sarcomas treated between 1986 and 1992 for whom complete studies including size and volume measurements and DNA ploidy determinations as assessed by flow cytometry were available, a search for a marker for increased risk of metastasis or death was performed. RESULTS: Grade of the lesion, sex, diagnosis, anatomical site, ploidic data (including mean DNA index and presence of an aneuploid peak), and treatment factors (including type of surgery, local recurrence, or radiation protocol) did not correlate with outcome. Age (younger patients did better), size (greatest diameter) and volume, and positive margins at surgery correlated with total survival. CONCLUSIONS: The results of the study, although negative, point out that using anatomical site, diagnosis, or ploidic analysis offers little toward anticipating outcome, whereas the size of the tumor is important.     

Childhood soft tissue sarcoma: a 20-year experience

PURPOSE: To evaluate the disease-free and overall survival of pediatric patients with nonrhabdomyosarcoma soft-tissue sarcomas. METHODS: We retrospectively analyzed the records of 67 pediatric patients with a diagnosis of nonrhabdomyosarcoma soft tissue sarcoma treated with curative intent between 1970 and 1992. Median follow-up time for the 52 survivors was 120 months (range, 7 to 277 months). Fifty-nine patients received external beam radiotherapy, in a median dose of 5400 cGy (range, 1800 to 6660 cGy.) All patients underwent an initial surgical procedure. Eighteen patients had gross residual disease, and 15 had gross total excision with microscopic residual disease or positive margins. Adjuvant chemotherapy was administered to 44 patients (65%). RESULTS: The actuarial 10-year freedom from progression or recurrence and overall survival rates were 76% and 75%, and the 20-year rates were the same. Of 18 patients with gross residual disease, 9 (50%) had local progression and 6 died of local-only disease. By contrast, only one patient with microscopic residual disease who received postoperative radiotherapy had a local recurrence. The disease-free survival rate also correlated with histologic grade. CONCLUSIONS: As with adult soft tissue sarcomas, gross residual disease predicts local failure. Our results suggest that pediatric patients with soft tissue sarcomas treated with surgery and postoperative radiotherapy generally have a favorable overall survival rate.     

Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues

The relationship between status of the surgical margin and local control of soft tissue sarcoma of the extremities by preoperative radiation therapy has been assessed in 132 consecutive patients from 1974 to 1988. The 5-year actuarial local control rate was 94% for all patients; the rates were 97% and 82% for the 104 tumors with negative margins and the 28 tumors with positive margins, respectively. The local control rate was independent of the extent of the negative margin. For primary sarcomas, the local control rates were 96%, 97%, and 100%, respectively, for margins that were negative at < or = 1 mm or > 1 mm, or the specimens were negative for tumor; for positive margins the result was 83%. The overall local control rate was lower (not significant) for recurrent than for primary sarcomas: 88% vs. 94%. On the other hand, when stratifying by margin status, no difference was observed in local control results, i.e.: (1) 97% and 91% for primary and recurrent tumors with negative margins, respectively, and (2) 83% and 80% for primary and recurrent tumors with positive margins, respectively. Local control was not significantly higher in those patients who were treated by surgical resection (S), radiation (RT), and re-excision of the previous tumor bed than in those whose radiation therapy was started after the biopsy and followed by one surgical resection. For primary sarcomas that were resected with negative margins the results were: 100% of 15 patients treated by S-RT-S and 96% of 75 patients treated by RT-S.     

Varioliform mucosal polypoid lesions in intestinal tract in a patient with adult T-cell leukemia

We have investigated the significance of local recurrence on survival in 173 patients with localised soft-tissue sarcomas of the limbs and of the trunk. The overall survival rates at five and ten years were 75.2% and 68.0%, respectively. After definitive surgery at our hospitals, there was local recurrence in 25 patients (14.5%). After inadequate operations elsewhere, there was a higher incidence of late local recurrence (28.3%), in comparison with those with primary tumours treated by us (9.0%), or patients referred to us immediately after inadequate surgery elsewhere (10.2%). Because of small numbers these differences in the survival rates were not statistically significantly different. Univariate survival analysis showed that local recurrence after definitive surgery (p = 0.006) together with the histological grade (p = 0.0002), the size of the tumour (p = 0.002), its depth in relation to deep fascia (p = 0.003), and the surgical margin (p = 0.0001) were the significant prognostic factors. Local recurrence at the initial presentation did not affect survival. Multivariate analysis showed that local recurrence after definitive surgery also lost its apparent prognostic significance.     

Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases

BACKGROUND: In order to improve management, the files and tissue sections of 28 cases of malignant peripheral nerve sheath tumors (MPNST) diagnosed at the University of Virginia Health Sciences Center between 1960 and 1990 were reviewed. METHODS: Clinical data tabulated included age, sex, race, the presence or absence of von Recklinghausen neurofibromatosis type 1 (NF-1), tumor size, tumor location, type of treatment, and status of surgical margins. Pathologic study included assessment of mitotic rate, divergent differentiation, cellular atypia, necrosis, and vascular reaction. RESULTS: The median disease-free survival time was 11 months, and the median overall survival time was 44 months. Overall survival and disease-free survival were significantly influenced by patient age, tumor location, tumor size, extent of surgery, and quality of margins. Patients with a family history of neurofibromatosis also had better disease-free survival. None of the other clinical variables correlated with survival. CONCLUSIONS: The authors recommended that patients with NF-1 be followed closely for MPNST development. For most cases, treatment should include aggressive surgery with wide surgical margins combined with adjuvant radiation therapy. Chemotherapy may have a role for treatment failures.     

Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma

Limb salvage surgery in patients with osteosarcoma is reported to cause a higher rate of local recurrences with a poorer chance of survival. It was the aim of the study to analyze differences between ablative and limb sparing surgery in patients with osteosarcoma who are treated with chemotherapy with respect to local and systemic tumor control and to determine independent prognostic factors. One hundred thirty consecutive patients younger than the age of 21 years who were operated on at the authors' institution for osteosarcoma of the extremities were reviewed. Histologic evaluations of surgical margins according to Enneking and coworkers revealed mostly wide (n = 109) and radical (n = 10) resection margins. The 5-year disease free survival rate was 60% for those patients treated by amputation and 71% for those treated by limb salvage. The overall local recurrence rate was 2.3%; 4.3% for ablation but only 1.2% for limb sparing surgeries. Multivariate analysis showed an independent effect of tumor volume, response to chemotherapy, and as expected, metastases at the time of diagnosis on overall survival. These data indicate that in patients where wide or radical tumor resection can be achieved, no difference in the outcome between ablative and limb sparing surgery occurred in local and systemic tumor control.     

Surgical aspects in the multidisciplinary treatment of soft tissue sarcomas

Sarcomas are rare malignant tumors with a large variety of histologic subtypes. The surgical approach depends more on the histologic grade, the size and the site of the tumor. Radiologic diagnosis relies predominantly on MR-imaging. Discernible improvements have taken place in soft tissue sarcoma patient survivorship and quality of life over the past 20 years, with overall 5-year survival currently at approximately 50-80%. The place of surgery in the treatment of soft-tissue sarcoma is defined in the light of a review of the recent literature. Radical surgical resection is the mainstay of therapy. Local recurrence is the most common type of failure. Local recurrence is resectable and limb preservations possible in the majority of patients. Survival after treatment of local recurrence is determined mainly by the grade and secondarily by the size of the tumor. The essential risk factor for local recurrence is the quality of surgical resection, defined by the definitive resection margins. A lateral safety margin of 5 cm and of 2 cm to the depth should be respected. In sarcoma of the extremity the compartment is defined based on clinical, radiographic, histopathologic and operative findings. The use of muscle flaps to fill the surgical defects can improve the functional result and reduce the complication rate. Only about 5% of the patients need amputation. Evaluation of functional results must be based on objective criteria. In retroperitoneal sarcoma the significant factors for determining prognosis are grade and completeness of exzision. Multidisciplinary treatment according to common protocols is essential. Shifts in treatment have taken place over the past decade, from single-modality treatment involving radical surgery with compartment resection to sophisticated limb-salvage strategies combined with radiation therapy. In case of inadequate surgery e.g. in a large tumor with positive margins in high-grade soft tissue sarcomas the addition of radiotherapy can improve local control, but cannot ensure that obtained by adequate surgery. Patients with large (greater than 5 cm), high grade soft tissue sarcoma are at high risk for distant recurrence and disease-related mortality. Investigations of combined modality therapy with newer chemotherapy agents and dose intensification treatment strategies are warranted.     

Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with malignant oral tumors after definitive megavoltage irradiation, to analyze prognostic factors for PFS time and patterns of failure, and to analyze the influence of tumor recurrence and development of metastasis on survival. DESIGN: Prospective clinical trial. ANIMALS: 105 dogs with squamous cell carcinoma, fibrosarcoma, or malignant melanoma of the oral cavity without evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's regression model to determine significant prognostic factors and by use of a competing risk model to determine the differential effects of prognostic factors on type of, and time to, failure. In 8% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 7.6% of the dogs, chronic radiation reactions, including bone necrosis and fistula formation, developed. RESULTS: Prognostic factors that independently affected PFS time were histologic type and tumor T stage. Histologic type significantly influenced pattern of failure, but not time to failure, whereas clinical stage significantly influenced time to failure, but not type of failure. CLINICAL IMPLICATIONS: Irradiation was a safe and effective treatment of malignant oral tumors. Because the local efficacy of radiation was influenced only by tumor size, early treatment of oral tumors should improve the prognosis. In dogs without tumor recurrence, systemic metastases, rather than regional metastases, limited long-term survival after radiation therapy.     

Osteosarcoma of the pelvis. Oncologic results of 40 patients

The cases of 40 patients with osteosarcoma of the pelvis treated between 1977 and 1994 were reviewed. The location of the tumor was ilium in 30 patients, ischium in four, pubis in one, and sacrum in five. Most (58%) of the tumors were of the chondroblastic subtype. Thirty patients had surgical excision of the tumors: 10 with hemipelvectomies and 20 with limb sparing procedures. A wide margin was achieved in 16 of 30 (53%) patients, including 12 of 14 who had no sacral tumor involvement. Positive margins occurred at the sacrum in 11 patients, lumbar vertebra in one, perirectal space in one, and contralateral pubic body in one. Macroscopic tumor emboli within the regional large vessels were found in seven patients. The incidence of local recurrence was 32%: 13% in wide excisions, 38% in marginal excisions, and 80% in intralesional excisions. The 1- and 5-year overall patient survivals were 73% and 34%, respectively. Patients who had a surgical excision of the primary tumor had a significantly better survival than did those treated without surgery (5-year survival; 41% and 10%, respectively). Tumor size, surgical excision of the primary tumor, surgical margin, and type of surgical procedure were the prognostic factors for patients with Stage IIB tumors.     

Prognostic importance of alkaline phosphatase activity in serum from dogs with appendicular osteosarcoma: 75 cases (1990-1996)

OBJECTIVE: To determine whether alkaline phosphatase activity in dogs with appendicular osteosarcoma can be used as a prognostic indicator. DESIGN: Retrospective study. ANIMALS: 75 dogs with appendicular osteosarcoma. PROCEDURE: Serum total alkaline phosphatase (TALP) and bone-specific alkaline phosphatase (BALP) activities were determined from archival serum samples obtained at various times during treatment of appendicular osteosarcoma and follow-up evaluations. Associations among activities of TALP and BALP and survival and disease-free intervals, percentage of bone length involved with tumor, histologic subtype, and method of surgical treatment were evaluated. RESULTS: High activities of TALP and BALP before surgery were significantly associated with shorter survival and disease-free intervals in dogs undergoing surgery (amputation or limb-sparing procedure) and adjuvant chemotherapy. Activity of BALP significantly decreased in 29 dogs for which postoperative samples were available. Failure of BALP activity to decrease after surgery was correlated with shorter survival and disease-free intervals. CLINICAL IMPLICATIONS: Activities of TALP and BALP in serum are important prognostic factors for appendicular osteosarcoma in dogs. Prognostic factors may help clinicians initiate more aggressive treatment for dogs that are at higher risk of death or relapse.     

Radiation therapy in the management of desmoid tumors

PURPOSE: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery. METHODS AND MATERIALS: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods. RESULTS: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05). CONCLUSIONS: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.     

Does the placement of surgical clips within the excision cavity influence local control for patients treated with breast-conserving surgery and irradiation

PURPOSE: A number of authors have demonstrated the importance of using surgical clips to define the tumor bed in the treatment planning of early-stage breast cancer. The clips have been useful in delineating the borders of the tangential fields, especially for very medial and very lateral lesions as the boost volume. If surgical clips better define the tumor bed, then a reduction in true or marginal recurrences should be appreciated. We sought to compare the incidence of breast recurrence in women with and without surgical clips, controlling for other recognized prognostic factors. METHODS AND MATERIALS: Between 1980 and 1992, 1364 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Median follow-up was 60 months. Median age was 55 years. Seventy-one percent of patients were path NO, 22% had one to three nodes, and 7% had > than four nodes. Sixty-one percent were ER positive and 44% PR positive. Margin status was negative in 62%, positive in 10%, close in 9%, and unknown in 19%. Fifty-seven percent of women underwent a reexcision. Adjuvant chemotherapy + tamoxifen was administered in 29%, and tamoxifen alone in 17%. Surgical clips were placed in the excision cavity in 556 patients, while the other 808 did not have clips placed. All patients had a boost of the tumor bed. Patients had their boost planned with CT scanning or stereo shift radiographs. No significant differences between the two groups were noted for median age, T stage, nodal status, race, ER/PR receptor status, region irradiated, or tumor location. Patients without clips had negative margins less often, a higher rate of unknown or positive margins and more often received no adjuvant therapy compared to patients with surgical clips. RESULTS: Twenty-five and 27 patients with and without surgical clips, respectively, developed a true or marginal recurrence in the treated breast. The actuarial probability of a breast recurrence was 2% at 5 years and 5% at 10 years for patients without clips compared to 5 and 11%, respectively, for patients with clips (p=0.01). Comparing the breast recurrence rates for patients with and without clips there was no significant difference for the following factors: chemotherapy, tamoxifen, negative, positive or close margins, reexcision, N1, and central or inner primary. Increased rates of breast recurrence were noted for patients with clips for the following variables: no adjuvant treatment (p < 0.001), unknown margins (p < 0.001), a single excision (p = 0.003), path NO (p = 0.001), and outer location (p= 0.02). A forward stepwise multivariate analysis for all 1364 patients was performed using the aforementioned variables as well as the presence or absence of surgical clips and the primary surgeon. The surgeon (p = 0.03) and no adjuvant treatment (p = 0.01) significantly influenced breast recurrence. For patients with surgical clips the 10 year isolated breast recurrence rate was 21% for a single surgeon vs. 6% in the remainder of the group (p = 0.01). For patients with clips, this surgeon had unknown margins in 48% of cases compared to 10% overall (p = 0.001). Excluding this surgeon from analysis the isolated breast recurrence for patients with clips was 6 vs. 5% for patients without clips (p = 0.18). CONCLUSIONS: Overall, there was a significant difference in the 10-year breast recurrence rate favoring women without clips despite more adverse prognostic factors. There was no difference in the breast recurrence rate for patients with or without surgical clips if careful attention to margin status was addressed. Failure to ink the surgical specimen resulting in unknown margins cannot be compensated for with the placement of .     

S-phase fraction of 155 soft tissue sarcomas: correlation with clinical outcome

BACKGROUND: Traditionally, grade is considered the most important prognostic factor for soft tissue sarcomas (STS). However, because of the alleged difficulties in reproducibility of grading, new, objectively determined prognostic factors would be of value. The aim of our study was to establish if S-phase fraction (SPF) measured with flow cytometry was of prognostic significance for STS. METHODS: In this study, we included all 193 adult STS patients with superficial trunk or limb tumors who were treated by the Helsinki University Central Hospital (HUCH) STS group between January 1987 and May 1993. One hundred and seventy-two formalin fixed paraffin embedded tumor samples were available. SPF measurement was successful in 155 cases. RESULTS: Eighty-six cases were diploid. Ploidy was found to have no effect on overall survival. The median SPF was 6.8% (diploid tumors, 4% and nondiploid tumors, 12.9%). A high SPF predicted a shorter survival in patients with diploid tumors (P=0.003). The prognostic value was even stronger when we studied disease specific survival and excluded from analysis samples that contained less than 50% tumor cells (P=0.011). However, no prognostic value could be detected in nondiploid tumors or in the material as a whole. CONCLUSIONS: Our results suggest that high SPF is an adverse prognostic factor for survival of patients with diploid STS. However, further studies are needed to confirm these results.     

Resectability of retroperitoneal sarcomas: a matter of surgical technique?

The management of retroperitoneal sarcomas has been hampered by the difficulty in complete resection, the resectability rate in the literature being about 53%. In a review of the last 88 consecutive patients with retroperitoneal sarcomas the resectability rate was 95%. At a mean follow-up of 48 months, the local recurrence rate was 17% following wide resection and 59% following local excision (P = 0.0002). For patients with minimum follow-up of 5 years, the local recurrence rate was 39% for those with primary tumours and 57% for those referred with local recurrence. Local recurrence diminished the rate of long-term survival. The 5- and 10-year survival rates for the primary retroperitoneal sarcomas (n = 55) were 66% and 57% and for those referred with locally recurrent sarcoma (n = 33) 57% and 26%, respectively. The 5-year survival rate varied significantly with the grade of the tumour, from 88% for Grade I to 44% for Grade III tumours (P = 0.006). In conclusion, with modern surgical techniques the resectability rate of retroperitoneal sarcomas is about 95%, and the survival rate of the primary tumours approximates that of the primary soft tissue sarcomas of the extremities.     

Coexistent minocycline-induced systemic lupus erythematosus and autoimmune hepatitis

BACKGROUND AND OBJECTIVES: The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor. METHODS: Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples. RESULTS: The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator. CONCLUSIONS: K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.     

Characteristics of non-participants and reasons for non-participation in a population survey in Kin-Hu, Kinmen

We analyzed the pattern of failure and clinicopathologic factors influencing the disease-free survival of 78 patients who died after macroscopic curative resection for pancreatic cancer. Local recurrence was a component of failure in 56 patients (71.8%) and hepatic recurrence in 48 (61.5%), both accounting for 97% of the total recurrence rate. About 95% of recurrences occurred by 24 months after operation. Median disease-free survival time was 8 months, and cumulative 1-, 3-, and 5-year actuarial disease-free survival rates were 66%, 7%, and 3%, respectively. Multivariate analysis showed that tumor grade (p = 0.04), microscopic radicality of resection (p = 0.04), lymph node status (p = 0.01), and size of the tumor (p = 0.005) were independent predictors of disease-free survival. Patterns of failure and disease-free survival were not statistically influenced by the type of surgical procedure performed. Median survival time from the detection of recurrence until death was 7 months for local recurrence versus 3 months for hepatic or local plus hepatic recurrence (p < 0.05). From our experience and the data collected from the literature, it appears that surgery alone is an inadequate treatment for cure in patients with pancreatic carcinoma. Effective adjuvant therapies are needed to improve locoregional control of pancreatic cancer after surgical resection.     

Pathologic correlates of prognosis in lymph node-positive breast carcinomas

BACKGROUND: Many pathologic features of breast carcinomas have been proposed as prognostic correlates; their interrelationships and their relative value as prognostic indicators were studied. METHODS: A series of 399 axillary lymph node-positive infiltrating ductal breast carcinomas was studied histologically and compared with the patient prognosis. RESULTS: Many pathologic findings fit into two groups of closely related features--those related to the extent of local spread and those related to histologic anaplasia and mitotic count. Both groups correlated with the primary tumor size. The best predictors of long-term survival were measures of the extent of axillary metastasis (the number of axillary metastases, the size of the largest metastasis, and lymph node capsular invasion), which are components of the pathologic node stage. The mitotic count, tumor grade, primary tumor stage, smooth tumor border, tumor necrosis, and multifocal primary tumors were weaker but significant survival correlates. The mitotic count and Bloom-Richardson grade best predicted the survival time of patients with node-positive disease who died. Four years after diagnosis, less than 25% of the patients who would die of breast carcinoma in the low mitotic count and Bloom-Richardson Grade 1 (well differentiated) groups already had died; more than 75% of those in the high mitotic count and Bloom-Richardson Grade 3 (poorly differentiated) groups already had died. Among patients with small tumors (< 1.8 cm in diameter), those with one micrometastasis (1-2 mm) had a worse prognosis than those with uninvolved lymph nodes of similar size. CONCLUSION: The extent of axillary metastasis best predicted the long-term prognosis of patients with infiltrating ductal carcinoma and axillary metastases. The mitotic count and tumor grade best predicted the survival time of those who died.     

Metastasis-free survival after local recurrence of soft-tissue sarcoma

We analysed metastasis-free survival after local recurrence in a population-based series of 432 patients treated for soft-tissue sarcoma of the extremities or trunk wall. Local recurrence was found in 124 patients; of these, 73 had no detectable metastases when the last local recurrence was diagnosed. No patient received chemotherapy for local recurrence. The 73 patients had a 5-year metastasis-free survival rate of 0.73 after the last local recurrence, compared with 0.47 in all 124 patients with local recurrence. The 5-year metastasis-free survival rate was 0.76 in the 308 patients who had never developed local recurrence, and 0.68 in the whole series. The selection of patients with local recurrence but no concurrent metastasis creates a subset of the population with a good prognosis; this makes it difficult to evaluate the effect of treatment for local recurrence on survival rate. In studies of prognosis this group of patients should be analysed separately from patients with primary tumours.     

Differential spatio-temporal expression of the insulin-like growth factor genes in regenerating sciatic nerve

BACKGROUND: Prognosis following locoregional recurrence of breast cancer after mastectomy often is described as fatal. However, certain subgroups with better prognosis are supposed. We analysed established prognostic factors for their influence on post recurrence survival in order to discriminate favourable from unfavourable subgroups. PATIENTS AND METHODS: Between 1979 and 1989 163 patients with a local or regional recurrence of breast cancer following mastectomy were treated at the Department of Radiation Oncology of the University of Würzburg. One hundred and forty had an isolated recurrence, without evidence of distant disease at the time of recurrence. Median follow up for patients alive at the time of analysis was 102 months from diagnosis of recurrence. Thirteen prognostic factors were tested. RESULTS: Out of the 140 patients 94 (58%) developed distant metastases within the follow-up period. Metastatic-free rate was 42% at 5 years and 38% at 10 years following recurrence. Recurrences occurred in 50% of patients within the first 2 years from primary surgery, in 83% within 5 years. In univariate analysis statistically significant influence on survival rates was found for pT, pN-status, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, hormonal receptor status, presence or development of distant metastases, time to recurrence and site and extension of recurrence. Two- and 5-year survival rates ranged from 64% to 81% and from 40% to 60%, respectively in the favourable subgroups compared to a survival rate ranging from 15% to 44% at 2 years and 0% to 29% at 5 years in the unfavourable subgroups. In patients with involved axillary lymph nodes, the absolute number of nodes did not prove to have significant influence on overall survival. Histopathological grading did not reach statistical significance levels although an influence on survival was observed. Preceding adjuvant radiotherapy did not influence post-recurrence survival rates. Also preceding adjuvant systemic therapy showed no significant impact on survival. Multivariate analysis demonstrated that primary axillary status correlated most strongly with overall survival (p < 0.001) followed by tumor necrosis (p < 0.01). CONCLUSIONS: The mentioned prognostic factors may be useful in determining the adequate (local and systemic) therapy and the best time for it. Our data support previous findings, that certain subgroups with favourable prognostic features exist and they might still have a chance for cure by an adequate local treatment, whereas subgroups of patients with unfavourable prognostic factors have to receive systemic therapy immediately following local therapy because of the forthcoming systemic progression.     

Postradiation sarcoma of bone: review of 78 Mayo Clinic cases

Postradiation sarcoma of bone is an uncommon but serious sequela of radiation therapy. Seventy-eight Mayo Clinic patients have been treated for sarcomas arising in irradiated bones. They received their initial radiotherapy for a wide variety of nonneoplastic and neoplastic conditions, both benign and malignant. Thirty-five sarcomas arose in bone that was normal at the time of radiotherapy, and 43 arose in irradiated preexisting osseous lesions. The latent period between radiotherapy and diagnosis of sarcoma averaged 14.3 years. Ninety percent of the postradiation sarcomas were either osteosarcomas or fibrosarcomas; chondrosarcoma, malignant (fibrous) histiocytoma, malignant lymphoma, Ewing's tumor, and metastasizing chondroblastoma also occurred. Prompt radical surgery, when feasible, is usually the treatment of choice for the sarcoma. About 30% of patients with sarcomas of the extremities or craniofacial bones survived 5 years without recurrence; there were no disease-free survivors among patients with tumors of the vertebral column, pelvis, or shoulder girdle. The low risk of sarcoma following radiotherapy for the treatment of cancer should not be a contraindication to its use in these patients; however, radiation therapy for benign bone tumors should be reserved for lesions that are not amenable to surgical treatment. An unusual case is also reported herein in which a fibrosarcoma was discovered in the humerus of a patient who had received radiotherapy 55 years previously for a verified osteosarcoma in the same site.