Marvin M. Romsdahl

The relationship between histopathology and tumor behavior was examined in 71 cases of chondrosarcoma. The tumors were grouped into Grades I, II, and III on the basis of mitotic rate, cellularity, and nuclear size. The five-year survival rates of Grades I, II, and III are 90%, 81%, and 43%, respectively, while the corresponding 10-year survival rates are 83%, 64%, and 29%. None of the Grade I chondrosarcomas metastasized, while metastasis was observed with 10% of the Grade II tumors and 71% of the Grade III tumors. No definite relationship between tumor grade and local recurrence was found. In addition, the significance of the extent of the original operative procedure was evaluated for chondrosarcoma, Grades I and II. Local recurrence which could not be controlled by additional surgery occurred in 46% of the patients treated initially by local excision, but in only 9.5% of those who were treated by amputation or resection of all or part of the involved bone. It is concluded that chondrosarcomas range from locally aggressive non-metastasizing neoplasms to high-grade malignancies with marked metastatic potential, and that these groups may be defined and separated by the use of histopathologic criteria. The rate of local recurrence, however, is primarily dependent on the adequacy of surgical therapy rather than histologic grade. Cancer 40:818–831, 1977.

From January 1963 through December 1977, 300 adults with soft-tissue sarcomas were treated by a conservative surgical excision and postoperative radiotherapy. The absolute two- and five-year disease-free survival rates are 74% (222/300) and 61.3% (103/168), respectively. The five-year survival rate varies with: (1) anatomic site, e.g., 69.4% (75/108) for extremity lesions vs. 33% (5/15) for abdominal lesions; (2) histopathologic diagnosis, e.g., 86.4% (19/22) for fibrosarcoma vs. 50% (15/30) for neurofibrosarcoma; and (3) stage of the lesion. The overall local recurrence rate was 22.3% (67/300) and 27% (81/300) of the patients developed distant metastases. The incidence of lymph node metastases as an initial site of spread was only 2.7% (8/300); therefore, elective treatment of the regional lymphatics is not indicated. The 6.5% incidence of significant complications in extremities is low and might be further diminished by careful treatment planning. The combination of conservative surgery and postoperative radiation therapy maintains a functional limb in 84.5% (169/200) of patients with extremity lesions. This rate is comparable to the five-year survival rate attained with radical surgery.

One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.

The appropriate surgical therapeutic options for either localized or more advanced disease in patients with gastrointestinal leiomyosarcomas remain unclear. A staging classification for this disease has not been adopted nor risk factors identifying patients at risk for recurrence defined. To address these issues, this study evaluated the influence of various clinicopathologic variables on overall and disease-free survival. In an univariate analysis of overall survival involving 191 patients, the Cox proportional hazards model identified four factors that were associated with a significantly better outcome: complete resection without tumor rupture (p less than 0.001), localized lesions (p less than 0.001), low grade of tumor (p = 0.02), and tumors smaller than 5 cm (p = 0.03). When interactive effects of these factors were taken into account, however, type of resection of the tumor was selected as the only significant prognostic factor in a multivariate analysis. Complete resection without tumor rupture improved overall survival of patients with localized disease (median, 46 months) as well as those with contiguous organ invasion (median, 36 months) or peritoneal implants (median, 36 months). In contrast, patients with incomplete resections survived for a median of 21 months. Patients with tumor rupture, despite removal of all gross disease, behaved similarly to those with incomplete resections; median survival was only 17 months. For disease-free survival, important determinants selected from a multivariate analysis were tumor rupture (p = 0.002), contiguous organ invasion (p = 0.02) and high tumor grade (p = 0.02). A staging classification incorporating these prognostic factors of significance was evaluated using a TGM system: T1 (less than 5 cm), T2 (greater than or equal to 5 cm), T3 (contiguous organ invasion or peritoneal implants), T4 (tumor rupture); G: G1 (low grade), G2 (high grade); M: M0 (no metastases), M1 (metastases present). The corresponding 5-year overall survivals for stages I, II, III, IVA, and IVB were 75%, 52%, 28%, 12%, and 7%. Disease-free survival at 2 years after surgery was 89%, 57%, and 47% for stages I, II, and III, respectively. In conclusion, surgery remains the primary modality of treatment for patients with gastrointestinal leiomyosarcomas, and complete resection of all disease without tumor rupture, even of locally advanced disease, improves overall and disease-free survival. A staging classification appears feasible and is recommended to determine outcome in patients with leiomyosarcomas arising from the gastrointestinal tract.

Summary The three malignant melanoma cell lines used are characterized by having high, intermediate , and low quantities of pigment production. The response of these malignant melanoma cells to X-ray in vitro does not correlate with a model of the classically radioresistant tumor cell that clinical experience might predict. The in vitro melanoma cells were only slightly more resistant to X-rays than the nontumor in vitro Chinese hamster ovary cell line tested. The responses to X-rays of all three melanoma lines were the same ( n = 40, D 0 = 100 rads). The response to ultraviolet light varied with the amount of pigment present in each cell line. The strain producing a high quantity of pigment was the most UV resistant ( n = 3, D 0 = 57 ergs/sq mm). The strain producing a low pigment quantity was the most UV sensitive ( n = 3, D 0 = 31 ergs/sq mm). All melanoma strains were more resistant to UV than the Chinese hamster ovary cell line ( n = 10, D 0 = 20 ergs/sq mm). Survival determinations made as a function of time between two fractionated UV doses of 100 + 100 ergs/sq mm indicated that these melanoma cells possessed ability to recover from sublethal UV damage.