Good Histologic Response Research Articles

Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.

Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.

Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases.

Between April 1990 and December 1994, we treated 24 patients with telangiectatic osteosarcoma (TO) of the extremities with neoadjuvant chemotherapy using 2 protocols. Surgery consisted of limb salvage in 21 patients and amputation or rotation plasty in 3. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 23 patients, of whom 12 had total necrosis. With a mean follow-up of 74 (60-96) months, 20 patients remained continuously free of disease and 4 relapsed with lung metastases. There were no local recurrences. Comparing these results to the ones achieved in 269 contemporary patients with conventional osteosarcoma of the extremities using the same protocols for chemotherapy, we found a significantly better histologic response to chemotherapy (96% vs 68% of good histologic response; p = 0.004) and disease-free survival (83% vs 55%; p = 0.01) in the TO group. We conclude that TO, once considered a lethal tumor, seems to be even more sensitive to chemotherapy than conventional osteosarcoma, and that most of these patients may be cured without amputation.

Neoadjuvant intra-arterial infusion chemotherapy combined with hormonal therapy for locally advanced breast cancer.

To determine the efficacy of combined neoadjuvant intra-arterial infusion chemotherapy and hormonal therapy for treating locally advanced breast cancer, we compared the outcomes of patients with or without this therapy, and also assessed histologic response. Ninety-four patients with locally advanced breast cancer (stage IIIa, 56; stage IIIb, 38). Nineteen stage IIIa and 17 stage IIIb patients received intra-arterial plus hormonal therapy while 37 stage IIIa and 21 stage IIIb patients with similar ages and follow-up durations did not. Treated patients received intra-arterial epirubicin plus oral medroxy-progesterone. Five-year disease-free survival rates were 77.5% for intra-arterially treated and 33.0% for other patients in stage IIIa, and 70.5% for intra-arterially treated and 38.1% for other patients in stage IIIb. Five-year overall survival rates were 94.4% for intra-arterially treated and 61.7% for other patients in stage IIIa, and 90.9% for intra-arterially treated and 56.3% for other patients in stage IIIb. Ten-year overall survival rates in stage IIIb were 90.9% for treated and 22.5% for other group patents. All differences were statistically significant (p<0.05). Good histologic response to intra-arterial therapy was seen in 75% of the primary tumors and 71% of involved lymph nodes. Neoadjuvant intra-arterial therapy with hormonal therapy yielded better survival rates than no intra-arterial therapy or our previous intra-arterial regimen.

A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma

Despite advances in the treatment of primary limb osteosarcoma, the outcome of patients with primary metastatic and axial skeletal disease remains poor. The European Osteosarcoma Intergroup have assessed a combination chemotherapy regimen consisting of ifosfamide (IFOS) 3 g/m2/dl-2, doxorubicin (DOX) 25 mg/m2/dl-3 i.v. bolus and cisplatin (CDDP) 100 mg/m2/dl. One hundred nine previously untreated patients with primary osteosarcoma were registered. Eligibility was confirmed in 103. At presentation, 45 eligible patients had metastatic disease, 15 axial skeletal primary tumours and 43 non-metastatic limb tumours. The major toxicities were myelosuppression (90%, grade 3 or 4) and nausea and vomiting (74%, grade 3 or 4). Overall mean relative dose intensity (RDI) was 80% (88% CDDP, 75% IFOS, 81% DOX). Clinical response as measured by reduction in tumour volume occurred in 36% (95% confidence interval (95% CI): 27%-47%) of primary tumours. Response of pulmonary metastases to chemotherapy was seen in 33% (95% CI: 19%-49%). Good histological response (> or = 90% necrosis of the tumour) occurred in 33% (95% CI: 22%-45%) of resected tumours. Five-year survival was 62% in limb-non-metastatic, 41% in axial skeletal and 16% in limb metastatic patients. This regimen is active in osteosarcoma but does not appear to be more active than the two-drug CDDP-DOX regimen currently recommended by EOI.

Prognostic factors in non-metastatic limb osteosarcoma: A 20-year experience of one center.

The purpose of this study was to evaluate the prognostic significance of variables in osteosarcoma. We performed a retrospective analysis of 35 patients with non-metastatic limb osteosarcoma that were treated between 1973 and 1994. The following variables were evaluated: age, sex, ethnic group, tumor histology and primary site, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels at diagnosis, treatment regimen, and the histologic response to treatment. Three variables showed significant correlation with prognosis: i) histologic response to preoperative treatment. Disease-free survival (DFS) was 89% in patients with grade III-IV histologic response after a median follow-up (MFU) of 64 months, 67% in patients with grade II after an MFU of 64 months, the patients with grade I response died within 15 months (p<0.0001); ii) treatment regimen. DFS was 83% after an MFU of 42 months, 62% after an MFU of 82 months, and 30% after an MFU of 177 months in patients treated by the 90's, 80's, and 70's protocols, respectively (p<0.05); iii) corrected ALP (cALP) levels at diagnosis. DFS was 78% after an MFU of 88 months in patients with cALP levels <200, and 32% after an MFU of 56 months in patients with cALP levels >200 (p=0.01). Low ALP levels, good histologic response to preoperative chemotherapy, and the new therapeutic regimen correlated with good prognosis in patients with osteosarcoma.

Response of DNA ploidy to chemotherapy in primary and metastatic lesions in human osteosarcomas

Primary and pulmonary metastatic and pulmonary metastatic tumors (two synchronous and seven metachronous metastases) in nine patients with osteosarcomas were studied by DNA cytofluorometry. All patients were treated with both pre and postoperative chemotherapy. The results showed that all five diploid osteosarcomas and three of the four aneuploid tumors did not markedly change their ploidy pattern after preoperative chemotherapy, and had almost the same ploidy patterns as the pulmonary metastatic lesions. Those eight tumors showed poor histologic response and chemoresistance by the doxorubicin binding assay. Only one aneuploid osteosarcoma showing good histologic response and chemosensitivity changed its ploidy pattern to diploid, with the disappearance of aneuploid tumor cells and its synchronous pulmonary metastatic tumor also showed conversion to a diploid pattern with massive tumor necrosis. It is evident that those tumors showing no change in their ploidy pattern after chemotherapy were resistant to the chemotherapy. Therefore, we conclude that regardless of whether the pulmonary metastatic tumors were synchronous or metachronous, they showed the same change in their ploidy pattern as well as their chemosensitivity as the primary human osteosarcoma from which they were derived.

Histological evaluation of the effects of intraarterial chemotherapy for advanced breast cancer: a long-term followup study with respect to the survival rate.

To evaluate the effects of intraarterial infusion chemotherapy (IAIC) for advanced breast cancer, we examined the grade of histological responses of preoperative IAIC on tumors at the time of operation and estimated the patients' prognoses for 19 years. IAIC was done preoperatively using timely epochal anticancer drugs on 105 patients with locally advanced (Stage IIIa, IIIb) and metastatic (Stage IV) breast cancer. The survival rate of the Stage IIIb patients who showed a good histological response (Grade IIb< or =) to IAIC was 68.1% for 5 years, and 62.4% for 10 years, respectively. This was in contrast to that of the patients classified as Stage IIIb who showed a poor histological response (Grade IIa> or =) to IAIC. On the other hand, there was no significant difference in the survival rates between the Stage IIIa and IV patients with good and poor histological responses to IAIC. However, the findings showed that a good histological response to IAIC reflected a prolonged survival while the Stage IIIb and IV patients acquired a "down clinical staging" by IAIC. These results strongly suggest that IAIC thus appears to be a useful modality in the multidisciplinary treatment of advanced breast cancer, especially for Stage IIIb patients.

Ifosfamide and Actinomycin-D, Added in the Induction Phase to Vincristine, Cyclophosphamide and Doxorubicin, Improve Histologic Response and Prognosis in Patients with Non Metastatic Ewing's Sarcoma of the Extremity

The role of ifosfamide as first-line chemotherapy treatment of non metastatic Ewing's sarcoma of the extremity is still under discussion. The purpose of this paper is to report the results achieved in a neoadjuvant protocol (REN-3) in which ifosfamide, added to the conventional VACA regimen, was employed since the induction phase. Induction chemotherapy consisted of vincristine, cyclophosphamide, doxorubicin, actinomycin-D and ifosfamide. After local treatment, patients received the drugs used in the induction phase and etopo-side. Between November 1991 and November 1994, 61 patients with non metastatic Ewing's sarcoma of the extremity were treated. Forty-nine patients underwent surgery and 73.5% of them had a good histologic response. At a median follow-up of 60 months (range 32-76), 48 patients (79%) remained continuously disease-free. The 5-year event-free and overall survival were 77% and 87%, respectively. These results were significantly better both in terms of histologic response or event-free and overall survival than those obtained in 58 patients with non metastatic Ewing's sarcoma of the extremity treated in a previous protocol (REN-2) in which the same drugs were used, but ifosfamide was employed only in the maintenance phase. The present study suggests the importance of early use of ifosfamide in the treatment of patients with non metastatic Ewing's sarcoma of the extremity.

Predictive Factors of Histological Response to Primary Chemotherapy in Ewing's Sarcoma

Clinicopathologic variables associated with a good histological response to primary chemotherapy in Ewing's sarcoma are identified. The histological response to preoperative chemotherapy in 243 cases of Ewing's sarcoma treated with neoadjuvant chemotherapy was analyzed in relation to different clinicopathological features (sex and age of the patients, tumor size, serum lactate dehydrogenase (LDH) levels, tumor site) and to the type and schedule of anticancer drugs delivered preoperatively according to three consecutive chemotherapy regimens. A higher rate of good responses was achieved with the use of ifosfamide and dactinomycin in addition to a conventional three-drug VAC regimen, suggesting that these drugs should be included from the beginning in neoadjuvant regimens for the treatment of Ewing's sarcoma. The analysis of event-free survival in 158 patients with a 4-year minimum follow-up confirmed that histological response to preoperative chemotherapy is a reliable predictor of outcome in Ewing's sarcoma.

Neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone and in osteosarcoma located in the extremities: Analogies and differences between the two tumors

Malignant fibrous histiocytoma (MFH) is a rare bone tumor usually treated like osteosarcoma. Studies on analogies and differences between the two tumors have seldom been reported. Between March 1982 and December 1994, 51 patients with high-grade MFH of bone and 390 with high-grade osteosarcoma were treated with the same regimen of neoadjuvant chemotherapy. All of the tumors in both groups were located in the limbs. Preoperative chemotherapy was performed according to three different, successively activated, regimens consisting of MTX/CDP intraarterially, MTX/CDP/ADM, and MTX/CDP/ADM//IFO. The rate of limb salvage was the same in both the MFH (92%) and osteosarcoma (85%) patients. MFH showed a statistically significantly lower rate of good histologic response, 90% or more tumor necrosis (27% vs. 67%, P = 0.00001) for all three regimens. Despite this low chemosensitivity, the disease-free survivals of the two neoplasms were similar (67% vs. 65%). In terms of histologic response to primary chemotherapy, MFH has a lower chemosensitivity than osteosarcoma. Nevertheless, the two tumors have similar prognoses when treated with chemotherapy regimens based on MTX, CDP, ADM and IFO.

Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy

Most of the studies of the treatment of non-metastatic osteosarcoma of the extremity have reported results in terms of probability of survival up to five years with a minimum follow-up of less than two to three years. Definition of reliable indicators of prognosis and predictive factors for survival require mature data derived from a long-term survival analysis. A review of 127 patients with non-metastatic osteosarcoma of the extremity, treated between March 1983 and June 1986, was performed. The treatment protocol consisted of primary chemotherapy with MTX (randomization to high vs. moderate dosages) and CDP followed by surgery. Postoperatively, patients with < 60% tumor necrosis received ADM and BCD; those with tumor necrosis > or = 60% < 90% (Fair Responders FR) were given MTX, CDP and ADM. Up to January 1984, patients with tumor necrosis > 90% received MTX and CDP only, and after then they were given the same treatment as for FR. A multivariate analysis to test predictive factors for survival was performed. With a median follow-up of 134 months (range 114-153), the 12-year DFS was 46%. A good histologic response, an LDH baseline value within the normal range, and the use of high-dose MTX were positive predictive factors for DFS. With a median time of observation for survivors of 130 months, the 12-year overall survival was 53%. None of the patients who relapsed with local or distant recurrences other than lung metastasis are now alive. Patients with a relapse-free interval longer than 24 months had a significantly better post-relapse survival than those with a shorter relapse-free interval (40% vs. 7%; P = 0.0159). All of the patients who were not surgically treated had disease progression and died within 40 months after the first recurrence. The surgically-treated patients had a 30% post-relapse survival probability. In non-metastatic osteosarcoma of the extremity, chemotherapy-induced tumor necrosis, the baseline LDH serum value and the use of HDMTX are significant predictive factors for DFS. The relapse-free interval and the possibility of metastasectomy are significant factors conditioning the post-relapse survival.

The outcome of advanced soft tissue sarcoma patients with complete tumour regression after either chemotherapy alone or chemotherapy plus surgery. The Scandinavian sarcoma group experience

The intensified induction regimens used and the potential use of high-dose consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has focused interest on the outcome of those patients who can achieve complete remission (CR) by current therapy. The files from four institutions with a special interest in STS were studied. 38 adult patients with advanced STS who were converted disease-free by either CT alone ( n = 14) or CT followed by surgery ( n = 24) were found. The median follow-up time was 29 months. The median disease-free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%. For patients who achieved CR by CT alone, and for patients who were converted to CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS 48%) and 10 months (26%) ( P = 0.07), respectively. The histological response to CT significantly predicted outcome in patients subjected to surgery (DFS P value 0.004, DSS P value 0.02). Patients who achieved CR by surgery shortly after having achieved a clinical partial response (PR with early surgery) did better than those who where converted to CR by surgery after protracted CT following a clinical PR (PR with late surgery) (DFS P value 0.02, DSS P value 0.1). Our results confirm that CT alone can induce prolonged DFS in rare patients with advanced STS. In patients subjected to surgery, a good histological response indicates improved outcome.

The Outcome of Advanced Soft Tissue Sarcoma Patients with Complete Tumour Regression after either Chemotherapy Alone or Chemotherapy Plus Surgery. The Scandinavian Sarcoma Group Experience

<h2>Abstract</h2> The intensified induction regimens used and the potential use of high-dose consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has focused interest on the outcome of those patients who can achieve complete remission (CR) by current therapy. The files from four institutions with a special interest in STS were studied. 38 adult patients with advanced STS who were converted disease-free by either CT alone (<i>n</i> = 14) or CT followed by surgery (<i>n</i> = 24) were found. The median follow-up time was 29 months. The median disease-free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%. For patients who achieved CR by CT alone, and for patients who were converted to CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS 48%) and 10 months (26%) (<i>P</i> = 0.07), respectively. The histological response to CT significantly predicted outcome in patients subjected to surgery (DFS <i>P</i> value 0.004, DSS <i>P</i> value 0.02). Patients who achieved CR by surgery shortly after having achieved a clinical partial response (PR with early surgery) did better than those who where converted to CR by surgery after protracted CT following a clinical PR (PR with late surgery) (DFS <i>P</i> value 0.02, DSS <i>P</i> value 0.1). Our results confirm that CT alone can induce prolonged DFS in rare patients with advanced STS. In patients subjected to surgery, a good histological response indicates improved outcome.

Metastatic Osteosarcoma: A Review of Current Issues in Systemic Treatment

Purpose. Original articles and abstracts published between January 1991 and January 1997 were selected according to specified criteria and reviewed to provide answers to five interesting questions about the systemic treatment of metastatic osteosarcoma. Results. (1) In patients with metastatic disease at presentation, what is the outcome after intensive multi-agent chemotherapy? Historically, survival has been poor, but may be improving with the use of ifosfamide-containing regimens. (2) Can response to new agents be evaluated better in patients who have received no previous chemotherapy? Based on limited data, this is probably true. (3) Is the response to neo-adjuvant chemotherapy, as determined by histopathology, similar for the primary tumor and synchronous pulmonary metastases? With intensive multi-agent chemotherapy, good histological response rates are in the range 70–90% for both groups. (4) What is the outcome, after intensive combined modality treatment with chemotherapy and surgery, in patients relapsing with metastases after previous adjuvant chemotherapy, and what are the important prognostic factors? Outcome is highly variable, but 5-year survival ranges between 25 and 50% and a good outcome is more likely if recurrent disease is limited to resectable lung metastases. (5) Can a biological agent (L-MTP-PE) prolong the time to relapse in patients with resected metastatic osteosarcoma? Preliminary data suggest that this is possible, but more studies are required.

Neoadjuvant Chemotherapy for Osseous Malignant Fibrous Histiocytoma of the Extremity: Results in 18 Cases and Comparison with 112 Contemporary Osteosarcoma Patients Treated with the Same Chemotherapy Regimen

Eigthteen patients with high grade malignant fibrous histiocytoma (MFH) of bone and 112 patients with high grade osteosarcoma (OS) of the extremity were treated with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2 cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good histologic response to preoperative chemotherapy (90% or more tumor necrosis) was significantly higher in patients with osteosarcoma than in patients with MFH (74% vs 28%; p<0.003). However, at a median follow-up of 38 months (range 25-61), the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%, OS 70.5%; p=ns). In patients with MFH, no local recurrences were registered, whereas in the osteosarcoma group there were 6 local relapses (5.%).The effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has been assessed during the last 15 years. The results of the present study seem to indicate that, in spite of a usually poor histologic response to preoperative treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.

Clinical relevance of Ki-67 expression in bone tumors

The availability of Ki-67 monoclonal antibody has opened new possibilities for an extensive analysis of cell kinetics in human neoplasms. Ki-67 antibody reveals a nuclear antigen that is expressed in proliferating but not in quiescent cells. Although the reliability of Ki-67 immunostaining has been evaluated in different tumor types, little information has been reported on bone neoplasms. Cell proliferation, as determined by Ki-67 expression, was measured by immunofluorescence on representative cytospins obtained from 205 patients with bone tumors. In each sample, the percentage of Ki-67-positive cells was quantified on at least 500 cells and expressed as Ki-67 labeling index (LI). Ki-67 LI was lower in benign and low grade lesions as compared with high grade malignant lesions. A correlation between Ki-67 LI and histologic grade was observed in osteosarcoma and chondrosarcoma. In osteosarcoma, among the 43 primary lesions included in this study, 30 patients, all treated with the same regimen of chemotherapy and limb-salvage surgery, were selected to establish the prognostic significance of cell proliferation. The Ki-67 labeling was higher in patients with a good histologic response to chemotherapy. However, at a 24-month follow-up, a worse prognosis was associated with a higher proliferative activity, whereas no correspondence was found between the histologic response to preoperative chemotherapy and the disease free survival, suggesting that in high grade osteosarcoma the biologic aggressiveness expressed by high levels of Ki-67 LI may be clinically more relevant than the responsiveness to antineoplastic agents. In bone tumors, the level of Ki-67 expression correlates with the level of malignancy and is diagnostically and prognostically useful.

Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients

28 patients with telangiectatic osteogenic sarcoma of the extremities were treated between March 1983 and March 1990 with neoadjuvant chemotherapy according to two different protocols activated successively. With the first protocol, patients preoperatively received high dose methotrexate (HDMTX)-cisplatinum (CDP) and postoperatively, depending on the histological response, either HDMTX-CDP-doxorubicin (ADM) or ADM-“BCD”. With the second protocol patients were preoperatively treated with HDMTX-CDP-ADM and postoperatively either with the same drugs or with the same drugs plus ifosfamide and VP-16. Preoperatively, CDP was delivered intraarterially. A good histological response (tumour necrosis >90%) was observed in 25 patients (89%) and at a mean follow-up of 5 years (2–9 years) 23 patients (82%) remained continuously disease-free and 5 developed lung metastases. These results are better than those obtained in 272 contemporary cases of conventional osteosarcoma of the extremities treated with the same protocols (62% good histological responses and 61% continuously disease-free survival).

口腔へん平上皮癌症例におけるｉｎｄｕｃｔｉｏｎ ｃｈｅｍｏｔｈｅｒａｐｙの意義に関する臨床病理学的研究

The purpose of this study was to assess the value of induction chemotherapy based on clinicopathologic malignancy grade in systematic oral cancer treatment. Onehundred and eight patients with oral squamous cell carcinomas were surgically operated on after induction chemotherapy based on both the clinicopathologic malignancy grade and the effect of induction chemotherapy. These cases were clinicopathologically examined to determine the value of induction chemotherapy. The following results were obtained:The clinical response rate of induction chemotherapy was 63.0% and the histologic response rate was 54. 6%. Regarding the relationship between the histologic effect and the clinicopathologic malignancy grade, as malignancy grade became higher the histologic response tended to diminish. Regarding the relationship between the histologic response and nodal metastasis, in the good histologic response group (GradeIII/IV) there were few primary metastases and no secondary metastases. It was suggested that induction chemotherapy which showed good anticancer efficacy at t4he primary region may also have a good effect on metastatic lymph nodes. Regarding the relationship between the histologic effect of induction chemotherapy and prognosis, the better the histologic response, the better was the prognosis. There was a statistically significant difference in prognosis between the histologic responder group (Grades II B/III/IV) and the histologic nonresponder group (Grades I/II A). These facts suggested that the histologic effects of induction chemotherapy may be one of the important factors determining prognosis. For survival rate by the clinicopathologic malignancy grade, the higher the malignancy grade, the lower was the survival rate. For survival rate by the clinical stage, the more advanced the stage, the lower was the survival rate. In particular, there was a statistically significant difference in survival rate between stage El and the other stages. The total five years' cumulative survival rate was 80.8%, which was favorable. This suggested that in systematic oral cancer treatment, induction chemotherapy and surgical therapy based on the clinicopathologic malignancy grade may help to improve the prognosis of oral cancer.In conclusion, induction chemotherapy was less effective for advanced and high malignancy grade case. Whereas it was more effective for the other cases. The application of both induction chemotherapy based on the clinicopathologic malignancy grade and surgery based on the effects of induction chemotherapy should help to improve chances for radical cure of oral cancer.

Serial Thallium-201 Scintigraphy in Osteosarcoma Correlation With Tumor Necrosis After Preoperative Chemotherapy

In 27 patients with extremity lesions (24 osteosarcoma, three malignant fibrous histiocytoma), a notable decrease in thallium-201 uptake was correlated with a good response to preoperative chemotherapy of the primary tumor. A good response is indicated by a greater than 95% tumor necrosis. Serial quantitative thallium-201 uptake of malignant bone tumors in patients receiving preoperative chemotherapy therefore can accurately predict a good histologic response and prognosis. Serial thallium scintigraphy can furthermore identify poor responses within two weeks after the initiation of treatment, or can prompt an early change in preoperative chemotherapy and facilitate limb salvage surgery.

Serum Methotrexate (MTX) Concentrations and Prognosis in Patients with Osteosarcoma of the Extremities Treated with a Multidrug Neoadjuvant Regimen

The relationship between the serum concentration of methotrexate and the prognosis has been studied in 108 patients with osteosarcoma of the extremities treated from September 1986 to December 1989 at the Chemotherapy Department of Rizzoli Hospital. The protocol of neoadjuvant chemotherapy included high doses of methotrexate (HDMTX) adriamycin, cisplatinum, ifosfamide and VP-16. After a median follow-up of 40.4 months (range 24-62), 84 (77.7%) of the patients studied remained continuously disease-free (CDF) and 24 relapsed. Significantly higher mean serum MTX concentrations were observed in the patients who remained CDF (669.5 mumol/l) than in the patients who relapsed (571.9 mumol/l) (p < .004). The breaking point of prognostic significance for the serum MTX levels seems to be 700 mumol/l. In fact, according to the mean MTX concentrations, the patients with less than 700 mumol/l showed a significantly lower disease-free survival than the patients with higher mean MTX concentrations (68.12% vs 94.87% p < .0013). The distribution of prognostic variables between the two groups was the same in terms of site and histological type of tumor and alkaline phosphatase serum levels at diagnosis. In the group which had more than 700 mumol/l MTX, a higher percentage of good histological response after primary chemotherapy was observed. This is probably independent from the MTX because no significant preoperative MTX serum levels between good and partially responding patients were observed.(ABSTRACT TRUNCATED AT 250 WORDS)