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Biomedical subjects

C Kosloff

Publications and source records attributed to C Kosloff.

18 recordsLinked to original sources
PubMed1989

Determinants of increased risk for recurrence in patients undergoing radical hysterectomy for stage IB and IIA carcinoma of the cervix.

From 1939 to 1977, 431 patients underwent radical hysterectomy as primary therapy for Stage IB or IIA carcinoma of the cervix at Memorial Sloan-Kettering Cancer Center. Only 11 patients were lost to follow-up at intervals of from 1 to 94 months. Assessment of gross and histologic extent of disease was correlated with the prevalence of nodal metastases and survival. Increasing tumor size, depth of invasion, and histologic grade were covariable and predictive of both lymph node metastases and recurrence. After stratifying for nodal metastases, adenocarcinoma cell type, the size of the primary tumor, depth of invasion into the cervix, and histologic grade were associated with decreased survival. For the 85 patients with documented recurrence of their carcinoma, the time to recurrence varied inversely with primary tumor size. Of 56 patients with documented recurrence and negative nodes at the time of their initial therapy, 10 patients (18%) were ultimately salvaged. None of the 29 patients with recurrent carcinoma and positive nodes at the time of their initial lymphadenectomy was successfully treated. Analysis of prognostic factors identifies a group of patients at high risk for recurrence and decreased survival for whom prospective trials of adjunctive treatment should be considered.

Adenocarcinoma↗
PubMed1982

Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy.

Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.

Antineoplastic Agents↗
PubMed1982

Impaired proliferative response to B-lymphocyte activators in common variable immunodeficiency.

The cell-mediated immune responses of 39 patients with common variable immunodeficiency (CVI) were studied in vitro, using Staphylococcus aureus and Escherichia coli prepared as whole cells and Candida albicans extract. These microbial activators wee found to require intact B-lymphocyte function for normal proliferative response. The patient group was observed to have significantly depressed lymphocyte responses compared wit those of controls studied in parallel (P less than 0.01). Negative lymphocyte response to one activator and strongly positive response to another were found in individual patients. Examination of patients' lymphocyte response to S. aureus and E. coli in association with serum IgG levels demonstrated that a rough correlation could be drawn, showing that patients with serum IgG less than 125 mg/dl had markedly lower (P less than 0.01) lymphocyte responses than those with serum IgG greater than 300 mg/dl. No similar correlation with phytohaemagglutinin activation was observed. Since depressed lymphocyte responses did not correlate with reduced B-cell number in these patients, intrinsic B-lymphocyte deficiency was indicated. These preparations of microbial activators are potentially useful tools in exploring lymphocyte subpopulation functions in primary immunodeficiency diseases.

Adolescent↗
PubMed1982

Cisplatin, doxorubicin, cyclophosphamide, and vindesine combination chemotherapy for non-small cell lung cancer.

Seventy-four patients with non-small cell lung cancer were treated in a prospective, randomized trial either with a four-drug combination of cisplatin, doxorubicin, cyclophosphamide, and vindesine (PACE) or with a three-drug combination of cisplatin, cyclophosphamide, and vindesine (PCE). None of these patients had received prior chemotherapy, and all had a Karnofsky performance status of at least 60. Of 68 evaluable patients, 21 (31%) had complete or partial remissions. Response rates for PACE and PCE were similar, and there was no difference in response rates for patients with adenocarcinoma or epidermoid cancer. The median duration of remission was 10 months (range, 2-26+); five patients are still in remission (median, 18+ months; range, 17+ to 26+). The median duration of survival for responding patients (complete or partial) was 18 months. Toxic effects, including mild to moderate myelosuppression, peripheral neuropathy, and nephrotoxicity, were manageable in general. The response rates and remission durations for PACE and PCE are similar to those seen with the two-drug combination of cisplatin and vindesine, and toxic effects are similar. Thus, the addition of doxorubicin and/or cyclophosphamide adds no advantage to the use of the cisplatin and vindesine combination alone.

Adenocarcinoma↗
PubMed1981

Combined modality therapy of esophageal carcinoma.

One hundred ten patients with epidermoid carcinoma of the esophagus were treated at the Memorial Sloan-Kettering Cancer Center (MSKCC) with combined modality techniques involving preoperative irradiation (RT) and surgery, and with preoperative chemotherapy (CT), surgery, and irradiation. For the 76 patients receiving preoperative RT during the period 1965-1976, the overall resectability rate was 54% with an operative mortality of 12%; long-term survivors (greater than 3 years) were few (7%). For 34 patients receiving preoperative CT with cisplatin and bleomycin, major objective tumor regression (greater than 50%) was seen by day 18 in 20%, with an additional 44% having smaller but definite improvement in the barium esophagram and in swallowing function. Of those receiving preoperative CT, 76% had resectable lesions, with an operative mortality of 11%. The median follow-up for this group is 24 months; of the 30 patients followed for at least 12 months, 20% are alive without evidence of disease. Although the resection rate following preoperative chemotherapy seems to be higher, thus allowing better palliation, neither preoperative radiation nor chemotherapy with cisplatin and bleomycin have had a major impact on long-term survival.

Adult↗
PubMed1981

Malignant schwannoma--clinical characteristics, survival, and response to therapy.

One hundred and sixty-five cases of malignant schwannoma were reviewed. Sixty-five (40%) of the patients had evidence of disseminated neurofibromatosis. Patients with neurofibromatosis were younger, had malignant schwannomas that were centrally rather than peripherally located, and had a shorter five-year survival (23%) than patients with solitary malignant schwannomas (47%). Histologically, tumors developing in patients with neurofibromatosis had a collagenous appearance, while tumors in patients without neurofibromatosis were undifferentiated and highly cellular. The clinical course of both groups of patients tended to be that of multiple local recurrences, although local recurrence had a more ominous prognosis in patients with neurofibromatosis. Chemotherapy responses in all these patients were extremely poor; however, the results of adjuvant therapy after surgery appeared encouraging. Fourteen patients (8.5%) had a malignant schwannoma in an area of prior radiation therapy and died of disease a median of 14 months after diagnosis. Malignant schwannoma should be considered in the differential diagnosis of tumors developing in areas previously treated with radiation.

Adolescent↗
PubMed1981

Ewing's sarcoma: ten-year experience with adjuvant chemotherapy.

Since May 1970, 67 consecutive patients with primary (nonmetastatic) Ewing's sarcoma were treated with adjuvant chemotherapy (CT) in addition to radiation therapy (RT) or surgery for the primary tumor. The first 19 patients were treated with four-drug sequential CT (T-2). The second protocol was a seven-drug induction combination CT (T-6) followed by T-2 maintenance CT; in both protocols CT was continued for 18 months. The current protocol (T-9) consists of combination CT given continuously for a period of 9 months. Of the entire group of 67 patients, 47 (70%) had axial and proximal lesions (pelvis, spine, rib, humerus, and femur) and 20 (30%) had distal lesions (forearm, leg, and foot); 53/67 (79%) are surviving free of disease 12--118 months (median 41 months) from the start of treatment. Fifteen of 23 (65%) patients with axial lesions, 19/24 (79%) patients with proximal lesions, and 19/20 (95%) patients with distal lesions are free of disease. Disease-free survivors include 28/39 (72%) male patients and 25/28 (89%) female patients. Thirty-four patients had RT, and 33 had surgery or surgery and RT, in addition to chemotherapy, for local treatment. The disease-free survival rate was 76% in the RT group and 82% in the surgery group; failure in the RT group was attributable to local recurrence in 7/34 (21%) patients. Recent experience with T-9 CT has demonstrated that CT given prior to RT or surgery can cause a great reduction in the size of the primary tumor while allowing the pathologically-eroded bone to heal prior to the initiation of RT; this also allows the high-risk patient with an axial primary (pelvis or spine) to tolerate the aggressive CT needed to prevent distant metastases. In addition to dramatically increasing survival in patients with Ewing's sarcoma, combination CT has helped achieve permanent local control. The superior survival rates for all sites of primary tumor are attributable to the early use of aggressive combination CT.

Antineoplastic Agents↗
PubMed1981

The role of local radiation in the treatment of non-Hodgkin lymphoma in children.

Eighty-one patients between 1 and 15 years of age with non-Hodgkin lymphoma were seen at Memorial Sloan-Kettering Cancer Center (MSKCC) in an 8-year period ending December 1973. There was no statistically significant difference among the survival distributions for site or histologic type. The patients also were divided into three groups according to the chemotherapeutic regimen employed in their care, and further subdivided as to whether they received "curative" radiotherapeutic attempts. Children treated with multiple agent chemotherapeutic regimen (LSA-2) did significantly better than children of the LSA-1 or nonprotocol (NP) group. Children with Stage I and Stage II disease did significantly better than children with Stage III and Stage IV disease. Radiation therapy as employed in this study prevented recurrence of local disease. All patients in whom the disease recurred died within a year from the appearance of recurrence. However, no statistically significant association between radiation and survival could be shown in this series.

Abdominal Neoplasms↗
PubMed1981

Defective cellular immune response in vitro in common variable immunodeficiency.

Mononuclear cells from 39 patients with hypogammaglobulinemia of the common variable type were analyzed for in vitro proliferative response to a panel of cell activators in order to examine the lymphocyte response to mitogens and to study the capacity to generate an immunologically specific secondary response. Patient lymphocyte response to phytohemagglutinin and concanavalin A was found to be significantly lower than that of controls studied in parallel (P less than 0.01), and low response did not correlate with T-lymphocyte number. Response to pokeweed mitogen was significantly lower than that of controls (P less than 0.01), but response to zinc, tested in a few patients, was normal. Strong depressions of patient lymphocyte proliferative responses to Candida albicans, Escherichia coli, and Staphylococcus aureus were observed (P less than 0.01); all of these microbial activators require intact B-cell function for maximum response. Repeated testing of individual patients indicated that poor lymphocyte response could be consistently observed. Examination of change in vitro lymphocyte response during clinical course and disease management showed that a consistent pattern of intrinsic lymphocyte functional deficiency could be demonstrated.

Adolescent↗
PubMed1981

Osteogenic sarcoma: eight-percent, three-year, disease-free survival with combination chemotherapy (T-7).

Sixty-one patients were treated with combination chemotherapy (T-7) for biopsy-proved, fully malignant, osteogenic sarcoma (OS) of the extremity. Chemotherapy consisted of the combination of bleomycin, cyclophosphamide, and dactinomycin, followed in 2 weeks by vincristine and high-dose methotrexate (HDMTX) given in doses of 8 g/m2 for adolescents and 12 g/m2 for children 12 years old or younger with citrovorum factor rescue. The HDMTX was administered weekly for 4 weeks. One week following the 4 HDMTX treatments, adriamycin (ADR) was given at a dose of 90 mg/m2 for 2 days. Two weeks after the ADR, 2 additional doses of HDMTX were given before surgery. Thirty-eight of the 61 patients were referred before amputation and underwent preoperative chemotherapy for approximately 3 months. After surgery, chemotherapy was resumed. Of the 61 consecutive patients with primary OS entered in the T-7 protocol, 54 (88%) remained free of disease for more than 8 to over 35 months (median 18+ mo), with a projected 3-year disease-free survival in excess of 80%. Of the 38 receiving T-7 chemotherapy before surgery, 28 demonstrated a near complete or complete lack of viable tumor cells on examination of the resected primary tumors. All 28 are surviving free of disease. Nine of the 10 patients less than 12 years of age remain free of disease from over 12 to more than 35 months (median 24+ mo). A significant increase in disease-free survival in the younger patients could presumably be attributed to the use of 12 g HDMTX/m2 in that age group. The prognostic value of the effect of preoperative chemotherapy on the primary tumor is statistically highly significant. These data indicated that preoperative chemotherapy with the proper dose of HDMTX would be valuable in all patients with OS.

Antineoplastic Agents↗
PubMed1981

Prognostic factors in the response of primary osteogenic sarcoma to preoperative chemotherapy (high-dose methotrexate with citrovorum factor).

Forty-three patients, ranging in age from 7 to 30 years (median age, 17 yr), with primary osteogenic sarcoma (OS), confirmed by biopsies and with no evidence of metastatic disease at the time of diagnosis, received T-7 chemotherapy for an average of 4 months before surgery, including high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR) (median, 7 courses), and 1 course each of bleomycin, cyclophosphamide, and dactinomycin, and adriamycin. At the time of definitive surgery, the surgical specimen showed a good histologic response to chemotherapy (grade III or IV response) in 29 (67%) of 43 patients and a poor histologic response (grade I or II response) in 14 (33%) of 43 patients. Among those who responded well, no patient relapsed, as all received a complete course of preoperative and postoperative chemotherapy for more than 5 to over 28 months after the initiation of treatment (medium, 13 mo). Among those who responded poorly, 6 of 14 patients relapsed with pulmonary metastases (a thoracotomy was beneficial to 1), 4 of 6 patients are alive with disease, and 1 patient died of progressive disease. On retrospective analysis, we observed that good and poor responders did not differ in the distribution of sex, age, race, primary site of disease, or histologic subtype of OS. An elevated alkaline phosphatase level that returned to normal under preoperative chemotherapy indicated a good response. Neither the 24-, 48-, and 72-hour serum MTX levels nor the fluid intake and urinary output during 3 days that followed HDMTX with CFR correlated significantly with tumor response. Based on our studies with this form of therapy, we concluded that the response of OS to preoperative chemotherapy is of prognostic value.

Adolescent↗
PubMed1981

Multidisciplinary treatment of advanced stages of embryonal rhabdomyosarcoma in children.

Twenty-eight previously untreated patients with embryonal rhabdomyosarcoma, stages II to IV, were treated with the T-6 induction protocol and maintained on the T-2 protocol. The T-6 protocol consisted of simultaneous administration of drugs and irradiation, given in 3 parts each separated by an obligatory period of rest. Twenty-four of the 28 patients (85.7%) survived 4 to 44 months, with a median follow-up of 24 months; 18 (64%) have been in continuous disease-free status. The immediate toxicity of the T-6 induction was severe and required intensive supportive care. To date, the results from the T-6 induction protocol were more effective than those achieved with the T-2 protocol.

Adolescent↗
PubMed1981

Multidisciplinary treatment of embryonal rhabdomyosarcoma in children: a progress report.

Fifty-nine patients under 21 years of age with embryonal rhabdomyosarcoma were treated according to a multidisciplinary protocol (T-2). The protocol consisted of surgical removal of the tumor, if possible, determination of clinicopathologic stages of the disease followed by radiotherapy for stages IB to IV, and chemotherapy. Radiation therapy was given in the range of 4,500--7,000 rad. The chemotherapy given for 2 years consisted of cycles of sequential administration of dactinomycin, adriamycin, vincristine, and cyclophosphamide. Forty-five of the patients (76%) are alive with no evidence of disease for 6 to 100 months (median follow-up of 57 ml). These include 19 of the 21 patients with stage IA (localized tumors, completely resected), 10 of the 10 stage IB (resected tumors, microscopic residual), 8 of the 9 stage II (unresectable tumors), 7 of the 14 stage III (unresectable tumors plus regional node involvement), and 1 of the 5 patients with stage IV (metastatic) disease. These results are superior to those achieved in 1960--70 at the Memorial Sloan-Kettering Cancer Center.

Adolescent↗
PubMed1980

Selection of operative procedure for adenocarcinoma of the midstomach. Twenty years' experience with implications for future treatment strategy.

Pathoanatomic studies of the regional spread of adenocarcinoma of the middle one-third of the stomach suggested the need for extensive gastric and lymphatic resection. To seek evidence of improved results, a retrospective study was made of 213 patients curatively treated by three commonly used procedures: 1) radical high subtotal gastrectomy (SG, n = 39), 2) radical total gastrectomy (TG, n = 48), and 3) extended total gastrectomy (ETG, n = 126). The overall five-year survival rates were SG:10%, TG:16%, and ETG:19%. Advanced stage tumors (N2, N3, or M1) were highly lethal, irrespective of the type of resection. However, patients with early stage tumors (T1-4, N0 or N1) showed higher survival rates after more extensive resections (ETG:42% and TG: six of eight patients, versus SG:17%). The highest survival rate (93%) was observed in a subset of patients with early stage tumors electively treated by ETG; this was achieved despite the presence of metastasis to the juxtagastric (N1) lymph nodes or direct invasion of an adjacent organ in most of these patients. These observations confirm the merit of extensive resection for carcinoma of the midstomach.

Adenocarcinoma↗
PubMed1979

Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery.

From 1973--1975, 31 patients with biopsied primary osteogenic sarcoma were treated with preoperative chemotherapy followed by surgical ablation of the primary tumor. Surgery was delayed in order to obtain a custom-fitted prosthetic bone implant in an attempt to avoid amputation. Preoperative chemotherapy included high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (T-5 protocol) and was administered for 3 months preoperatively and continued with the inclusion of cyclophosphamide for approximately 5 months postoperatively. At a follow-up period of 30--52 months, 23 of 31 patients (75%) are surviving (21 of 23 with no evidence of disease). Histologic examination of primary tumor removed at surgery revealed varying degrees of tumor destruction (from very little effect to no evidence of viable tumor) attributable to the effect of chemotherapy. The 21 patients that are disease-free survivors had a more complete effect of preoperative chemotherapy on the primary tumor. Some patients achieving favorable effects upon the primary tumor did so only after the dose of HDMTX was escalated to greater than the starting dose of 8 g/m2. Preoperative chemotherapy for all patients with osteogenic sarcoma would seem to offer the following advantages: 1) Evaluation of the effect of HDMTX with CFR on the primary tumor with escalation of the dose of HDMTX until a clinical response is observed, thus defining the dose of HDMTX effective in that patient, to be continued postoperatively as adjuvant therapy; 2) The early use of systemic therapy to eradicate distant microfoci of disease that will eventually kill the patient if not adequately treated by effective chemotherapy; 3) Allow more time for postoperative healing without the need to start adjuvant chemotherapy immediately; and 4) Provide the surgeon time to plan resection surgery. To date, 20 additional patients with biopsy proven osteogenic sarcoma have been treated with more aggressive preoperative chemotherapy (T-7) for approximately 2 1/2 months prior to definitive surgery (resection or amputation). Doses of HDMTX were escalated where necessary and good clinical responses were obtained in 19 of 20 patients. In the majority of patients, no evidence of viable tumor was found on histologic examination of the surgically removed primary tumor. All 20 patients are surviving free of active disease at this brief follow-up period of 4--20 months.

Adolescent↗