Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine

This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20-41) and 285 days (range 50-1,240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients.     

Organ preservation with interstitial radiation for base of tongue cancer

Management options for squamous cell carcinoma of the base of tongue include surgical resection (often with adjuvant radiation), definitive external radiation and external combined with interstitial radiation. The reported series is a single institution experience with interstitial radiation for base of tongue cancer. Twenty patients were treated definitively with interstitial radiation as a boost to external radiation, and four patients were treated palliatively with interstitial radiation alone for recurrent base of tongue cancers or disease arising in a previously irradiated base of tongue. Patient, tumor, and treatment details were analyzed relative to disease control and posttreatment patient function. The 5-year actuarial local control, locoregional control, distant metastasis-free survival, overall disease-free survival, and actuarial overall survival of the definitively treated patients were 86%, 84%, 57%, 41%, and 30%, respectively. The 5-year actuarial rate of tolerating a normal diet was 86%, and all long-term survivors had normal speech function. Of the four patients treated palliatively with interstitial implant alone for recurrent disease (three patients), or a second primary cancer in a previously irradiated site (one patient), local control was obtained in three and long-term disease-free survival was obtained in one. Interstitial implantation combined with external radiation is associated with a high rate of disease eradication with preservation of speech and swallow function. Interstitial radiation alone can achieve effective palliation.     

The role of chemotherapy as an adjuvant to surgery in the initial treatment of primary soft tissue sarcomas in adults

A prospective study was carried out to determine the results of chemotherapy as an adjuvant to surgery in the initial treatment of adult primary soft tissue sarcomas. The results were compared with those in a group of patients with similar histologic types of primary sarcoma treated by surgery alone. The chemotherapy regimen consisted of adriamycin, 60 mg/m2 intravenously on Day 1, and DTIC, 250 mg/m2 on Days 1 through 5. The cycle was repeated every 22 days. The total dose of adriamycin was 500 mg/m2; the DTIC was continued for 1 year. The adjuvant chemotherapy group consisted of 113 patients (group one) and the concurrent surgical resection group consisted of 144 patients (group two). In group one, 53 tumors were T1 and 60 tumors were T2; 67 of the tumors were grade 3 and 46 were grade 4. In group two, 65 had T1 and 79 had T2 tumors; 82 tumors were grade 3 and 62 were grade 4. The anatomic location and histologic types were similar in both groups. Seventy-seven (77%) of the 113 patients in group one lived disease free for 2 years, compared with 59% of the 144 patients treated by resection alone. Of the patients eligible for 5-year survival analysis, 74% were disease free in the adjuvant chemotherapy group, compared to 50% in the surgical group. The incidence of local recurrence was about the same in both groups. From a histologic standpoint, malignant fibrous histiocytomas and myogenic sarcomas appeared to benefit most with use of the use of the two-drug regimen used here, and the least favorable response was in liposarcomas and fibrosarcomas. In other histologic types, the role of adjuvant chemotherapy needs further clarification.     

软组织恶性纤维组织细胞瘤的放射治疗：附12例报告

本文报告12例软组织纤维组织细胞瘤的放疗结果,除1例单纯放疗外,首次术后辅助性放疗4例,其余7例为复发病例,其中2例单行放疗,2例再次手术,2例3次手术及1例5次手术后放疗。放疗剂量除1例因3次手术复发行术前照射2200cGy后而行截肢者外,其余病例为3354～7000cGy/24～40天。全组12例中6例生存1～3年,1例口咽部患者单纯放疗后健在4年余,其余4例无瘤生存5年以上,1例放疗后9个月死于肺转移。本文认为术后放疗可降低局部复发率,有些病例单纯放疗也可治愈,值得进一步探讨。     

Cryosurgical treatment of sacrococcygeal chordoma. Report of four cases

Sacrococcygeal chordoma is a rare malignant neoplasm situated in a location adjacent to important structures. Distant metastases are usually rare and occur late. The treatment of choice usually consists of radical surgery, sometimes followed by radiotherapy. Extensive surgical resection is difficult and often causes bladder and/or bowel dysfunction, and the local recurrence rate remains high. In an attempt to diminish both risks, the authors introduced cryosurgery in situ as a new treatment modality for chordoma in the sacrococcygeal region. From 1974 to 1980, four patients (two male, two female) with sacrococcygeal chordoma were treated with cryosurgery without resection. Two patients had extensive tumors (greater than 10 cm) and could be treated only palliatively. Two other patients with smaller tumors (less than 10 cm) had radical cryosurgical treatment. Both patients are disease-free 10 and 7 years after cryosurgical treatment. One of the palliatively treated patients is alive with local recurrence 4 years after cryosurgery, the other died of tumor after 5 years. In a cryosurgical lesion, the tissue is completely devitalized; however, the architecture of the tissue in peripheral nerves, large vessels, and bone is preserved and remains as a perfect autograft. Frozen tissue is very susceptible to the hematogenous spread of infection. Therefore, infection prevention is of utmost importance. The authors believe that cryosurgery should have a place in the treatment of sacrococcygeal chordoma.     

Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441).

The effectiveness of DTIC in the treatment of Grade III and IV astrocytomas was analyzed in two phases. In the first phase, 14 patients (Group A) with progressive neurologic dysfunction following primary treatment were treated with DTIC alone (8 patients) or in combination with CCNU or methyl CCNU (6 patients) and evaluated for change in neurologic status. Five of the 8 treated with DTIC responded symptomatically for a median duration of 18 weeks, and 3 of 6 treated with the combination of drugs responded for a median duration of 12 weeks. In the second phase, 15 patients (Group B) were treated within 4 weeks of surgical resection with radiation therapy and adjuvant chemotherapy with DTIC and/or MeCCNU. These patients were followed for survival and compared to a historical control group of 15 patients (Group C) treated with surgery and radiation only. The drug-treated group had a median survival of 55 weeks, compared to 35 weeks for the control group. Hematologic toxicity was life threatening in 2 of 14 patients treated with combination drugs, but mild with DTIC alone. DTIC appears to be active against malignant astrocytomas. Survival may be lengthened by combining chemotherapy with surgery and radiation therapy.     

Urine excretion of 5-S-cysteinyldopa and serum sialic acid as tumor markers in human melanomas

This study examines 5-S-cysteinyldopa, which is a melanoma-associated marker, and sialic acid whose increase appears to be a common feature of numerous cancers. In spite of some interferences due to sun exposure, 5-S-cysteinyldopa seems a significant indicator of metastases; the difference between 46 metastasis-negative and 34 metastasis-positive melanomas is significant at P less than 0.001. Cerebral metastases give little or no increase. In contrast with the 75% of patients who keep normal 5-S-cysteinyldopa excretion, all melanoma patients have elevated sialic acid. No difference occurs between glycoprotein carbohydrates of controls and patients after pronase digestion and con A chromatography. The use of those two parameters in association is proposed to have a proper index of tumor burden or success of therapy.     

Breast-conserving surgery and selective adjuvant radiation therapy for stage I and II breast cancer.

In this report we update our experience with selective adjuvant radiotherapy (XRT) following breast-conserving surgery (BCS) for early breast cancer. Of 150 evaluable private breast cancer patients treated by BCS since 1975, 83 were offered the option of foregoing adjuvant XRT because their primary disease met four pathological criteria: primary tumor less than or equal to 2.5 cm; adequate resection margins; no intramammary vascular, lymphatic, or perineural invasion by tumor; and minimal or no associated in situ cancer. Of the 67 patients who chose not to have XRT, four have developed local (breast) tumour recurrence at 80 months' median follow-up (5-year local recurrence rate 6.4% by Kaplan-Meier analysis). These findings are discussed in light of other series in which patients were carefully selected for BCS without XRT, and the observations of large randomized trials and unselected series of patients. We conclude that adjuvant XRT is not always necessary following BCS. The most valuable contribution of XRT to breast-conserving therapy is that a much larger proportion of breast cancer patients can be considered for conservative locoregional surgery than would otherwise be reasonable.     

Adjuvant chemotherapy of malignant melanoma. A pilot study

In a pilot study, 26 patients with stage I malignant melanoma, tumor thickness greater than 2.25 mm, and/or Clark level IV, and Stage II tumors were randomized to adjuvant chemotherapy with either DTIC, DTIC/CCNU/vincristine, or to a control group with no further treatment after surgery. The chemotherapy group contained 17 patients and the control group nine patients. The follow-up time is 37-54 months. The recurrence-free and overall survival is significantly longer in the patient group treated with adjuvant chemotherapy as compared to controls (p less than 0.025, according to the log-rank test).     

Phase II study of cisplatin and dacarbazine for metastatic colorectal carcinoma resistant to 5-fluorouracil.

Twenty-six patients with metastatic colorectal cancer were given cisplatin (CDDP) and dacarbazine (DTIC). Patients who relapsed while receiving adjuvant 5-fluorouracil (FU) or had 5-FU-resistant metastatic disease were included. Median age was 52 years and the male-to-female ratio was 1. Performance status (ECOG) was 3 in 5 patients and 0-2 in the remainder. CDDP (20 mg/m2/day i.v.) and DTIC were given (250 mg/m2/day i.v.) on days 1-5. The treatment was repeated every 3 weeks until disease progression. Total response rate was 19.2% (95% confidence interval: 4.5-34.3%) with one clinical complete response (3.8%) and 4 partial responses (15.4%). Median response duration was 5 months. Median survival for the whole group and for responders was 6 and 8 months, respectively. In conclusion, CDDP + DTIC combination has modest activity in patients with colorectal cancer resistant to 5-FU treatment.     

Treatment of advanced malignant hemangiopericytoma with combination adriamycin and DTIC: a report of four cases

One patient with a large inoperable malignant hemangiopericytoma and three patients with local recurrence and/or metastases were treated with combination adriamycin, 50 mg/m2, and DTIC, 600-700 mg/m2, intravenously every 4 weeks. Two achieved palliation, one with measureable shrinkage of tumor, and the other with loss of incapacitating lower limb edema secondary to vascular and lymphatic obstruction. The third patient objectively had a less than partial response. The fourth patient did not respond to adriamycin and DTIC or to a subsequent trial of cis-platinum, 60 mg/m2, intravenously every 3 weeks. However, radiotherapy produced an objective response at the site of the local recurrence and relief of painful bone metastases. Two patients died of progressive disease; the third patient has stable disease and is continuing chemotherapy; and the fourth patient died, probably from adriamycin-induced cardiac failure in the presence of rapidly advancing intraabdominal metastases. The combination of adriamycin and DTIC is active in malignant hemangiopericytoma, and palliation of advanced disease can be achieved. However, prolonged survival is uncommon in the presence of a large tumor burden.     

Premenopausal breast cancer patients treated with conservative surgery, radiotherapy and adjuvant chemotherapy have a low risk of local failure

The use of adjuvant chemotherapy in premenopausal breast cancer patients with positive nodes is now routine, but the optimal local treatment of these patients is uncertain. To determine the effect of adjuvant chemotherapy on the likelihood of local recurrence as the first site of failure in premenopausal patients treated with conservative surgery (CS) and radiotherapy (RT), we examined the outcome of 74 patients treated with CS, RT, and adjuvant chemotherapy and compared it to the outcome in 192 patients treated with CS and RT alone. Adjuvant chemotherapy consisted of four or more cycles of either a doxorubicin-containing regimen or cyclophosphamide, methotrexate, and 5-fluorouracil. All patients were less than 50 years old, had UICC-AJCC Stage I or II breast cancer treated between 1968 and 1981, had gross excision of the primary tumor, and had a total radiation dose to the primary tumor bed of greater than or equal to 6000 cGy. Factors predicting for local recurrence, such as extensive intraductal carcinoma and age less than 35, were equivalent in the two groups. Women treated with adjuvant chemotherapy had significantly worse T- and N-stages than women treated with conservative surgery and radiotherapy alone: 61% versus 36% had T2 tumors (p = 0.0003), 34% versus 6% had clinically positive nodes (p less than 0.0001), and 97% versus 4% had pathologically positive nodes (p less than 0.0001). Despite the poorer prognosis of patients treated with adjuvant chemotherapy, within 5 years of diagnosis, 4% of patients who received adjuvant chemotherapy had their initial relapse in the breast and 24% had initial failure elsewhere, compared with 15% local failure first and 14% failure elsewhere first for those treated without chemotherapy (p = 0.01). We conclude that premenopausal patients with positive nodes treated with combined modality therapy (conservative surgery, radiation therapy, and adjuvant chemotherapy) have a low risk of local recurrence as a first site of failure. These results suggest a possible interaction between radiation therapy and chemotherapy in their effects on local tumor control.     

Alteration of dacarbazine pharmacokinetics after interleukin-2 administration in melanoma patients

Summary In an effort to improve the treatment of metastatic malignant melanoma, we evaluated the sequential administration of the chemotherapeutic agent dacarbazine (DTIC) and the biological response modifier interleukin-2 (rIL-2) in a phase I–II study. Since the combination of biological response modifiers and chemotherapeutic agents could alter drug disposition, we evaluated the pharmacokinetics of DTIC and its major metabolite, 5-aminoimidazole 4-carboxamide (AIC), before and after rIL-2 administration. DTIC (1 g/m², 24-h i.v. infusion) was given on day 1 and rIL-2 (2–4 million Cetus units/m², 30-min i.v. injection), on days 15–19 and 22–26 of each course of therapy. The second DTIC dose was given on day 29, i.e., 3 days after the last rIL-2 administration. DTIC and AIC were assayed by reversed-phase HPLC. DTIC plasma levels showed a significant decrease after rIL-2 administration as compared with DTIC values obtained in the same patients before rIL-2 administration. DTIC area under the curve (AUC) values obtained after rIL-2 were lower than those obtained on day 1 before rIL-2 administration (P=0.02). After rIL-2, the total body clearance (Cl_T) was increased (P=0.04), as was the volume of distribution at steady state (V_ss;P=0.02). The decrease in AUC after rIL-2 administration became more pronounced as the rIL-2 dose was increased (P=0.03). No significant difference was detected in the elimination phase of DTIC when halflives obtained before and after rIL-2 administration were compared; the mean half-lives were 0.7 and 2.8 h for the - and -phases, respectively. The model-independent mean residence time was 3.4 h. The plasma AUC for the metabolite AIC did not charge after rIL-2 administration. AIC biphasic plasma elimination was also similar after rIL-2 administration, with - and -half-lives of 0.7 and 11.4 h, respectively. Urinary excretion of DTIC and AIC did not differ after rIL-2 administration; the overall DTIC excretion was 39% of the dose over 48 h, and AIC urinary excretion was 25% of the DTIC dose. The observed decrease in the DTIC plasma AUC after rIL-2 administration appears to be due to an increase in the volume of distribution, since other factors such as half-lives, urinary excretion, and metabolism were not significantly altered. The clinical consequences of the rIL-2-DTIC interaction remain difficult to assess based on presently available data, but this drug interaction should be taken into consideration in the development of future chemo-immunotherapy regimens that include high-dose rIL-2.This study was supported by a contract from Cetus Corporation (Emeryville, California) and by Wayne State University Ben Kasle Trust Fund for Cancer Research     

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults.

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 Mg/M² day 1, Adriamycin (ADR) 60 mg/M² day 2, and DTIC 400 Mg/M² days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M². Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000–5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500–2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy.The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8–41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment.     

Role of brachytherapy in the management of desmoid tumors

From 1977 to 1982, fourteen patients with desmoid tumors underwent surgery and brachytherapy. Surgery ranged from biopsy to complete or partial excision of the tumor. Most of these patients had locally advanced tumor or positive margins. A high recurrence rate is expected in such a group if treated by surgery alone. In twelve out of fourteen patients the treatment was considered curative when all disease sites could be encompassed. In the remaining two patients the treatment was considered palliative because the tumor encroaching on to the spinal cord was left untreated. Ten out of twelve curatively treated patients have remained free of recurrence at a minimum of 2 year follow-up. Five of them were followed from 4-6 years. In the palliatively treated group, one patient is alive with active disease at 18 months. Three patients developed complications with wound healing. This experience suggests that surgery and brachytherapy treatment for desmoid tumor results in higher local control than expected from surgery alone in this selected group of patients.     

Gene‐expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil‐based adjuvant chemotherapy

Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high‐risk patients. This study was aimed to identify a gene‐expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5′fluoruracil (5FU)‐based adjuvant chemotherapy. Two‐hundred and twenty‐eight patients diagnosed with Stages II–III colon cancer and treated with surgical resection and 5FU‐based adjuvant chemotherapy were included. RNA was extracted from formalin‐fixed, paraffin‐embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT‐qPCR. A tumor recurrence predicting model, including clinico‐pathological variables and gene‐expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71–4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12–6.42; p = 0.03). Identification of a new gene‐expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU‐based chemotherapy, and its combination in a robust, easy‐to‐use and reliable algorithm may contribute to tailor treatment and surveillance strategies.     

Correlation of clinical and pathologic features with outcome in patients with ductal carcinoma in situ of the breast treated with breast-conserving surgery and radiotherapy

: Although breast-conserving surgery followed by radiotherapy (RT) has become a standard treatment option for patients with ductal carcinoma in situ of the breast, risk factors for ipsilateral breast tumor recurrence (IBTR) in these patients remain an active area of investigation. The purpose of this study was to evaluate the impact of clinical and pathologic features on long-term outcome in a cohort of DCIS patients treated with breast-conserving surgery plus RT.

: Between 1973 and 1998, 230 patients with DCIS were treated with breast-conserving surgery plus RT at our institution. All patients were treated by local excision followed by RT to the breast to a total median tumor bed dose of 64 Gy. Adjuvant hormonal therapy was used in only 20 patients (9%). All available clinical, pathologic, and outcome data, including ipsilateral and contralateral events, were entered into a computerized database. The clinical and pathologic variables evaluated included detection method, mammographic appearance, age, family history, histologic subtype, presence of necrosis, nuclear grade, final margin status, and use of adjuvant hormonal therapy.

: As of December 15, 2000, with a median follow-up of 8.2 years, 17 patients had developed a recurrence in the ipsilateral breast, resulting in a 5- and 10-year IBTR rate of 5% and 13%, respectively. Contralateral breast cancer developed in 8 patients, resulting in a 10-year contralateral recurrence rate of 5%. Patient age, family history, histologic subtype, margin status, and tumor grade were not significantly associated with recurrence on univariate analysis. A significantly higher rate of local relapse was observed in patients with the presence of necrosis. The 10-year relapse rate was 22% in 88 patients with necrosis compared with 7% in 142 patients without necrosis (p <0.01). In multivariate analysis, the presence of necrosis remained a significant predictor of local relapse. No breast relapses occurred among the 8 patients with positive margins, and three relapses developed among 21 patients with close margins. The rate of IBTR in those with close/positive margins did not differ from the rate in those with negative or unknown margins. It is also notable that none of the 20 patients treated with adjuvant tamoxifen had developed IBTR or a contralateral event to date, although the follow-up on this group was still too short to reach significance.

: In this cohort of uniformly treated patients with a relatively long follow-up, the presence of necrosis was a significant predictor of local relapse. However, positive or close margin status was not a significant predictor of local relapse. Although none of the patients receiving tamoxifen had a recurrence in the ipsilateral or contralateral breast, longer follow-up is required to assess the effect of tamoxifen on these end points.     

Secondary cytotoxic response in vitro against Moloney lymphoma cells antigenically altered by drug treatment in vivo.

Cell-mediated cytotoxic response in vitro to a Moloney strain of murine leukemia virus-induced tumor (LSTRA) altered by 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was investigated with the use of mixed-leukocyte tumor cell cultures (MLTC). As assessed by means of a short-term 51Cr-release assay, minimal or no cytolytic activity was generated in primary MLTC. In contrast, high specific cytotoxic response against the altered tumor was obtained in secondary MLTC. Partial cross reactivity was found between the LSTRA and LSTRA/DTIC tumor lines.     

Postoperative vaginal radiation in endometrial cancer using a remote afterloading technique

Carcinoma of the endometrium is the most common malignancy of the female genital tract. In early stage endometrial cancer, surgery remains the primary mode of treatment while radiation therapy plays an adjuvant role. Prophylactic vaginal radiation has been shown to reduce significantly the incidence of vaginal recurrences. Between the years 1969-1976, 330 patients with FIGO Stages I and II endometrial cancer were treated according to a standard departmental policy in which 40 Gy of external radiation was given to high risk Stage I and all Stage II patients in combination with surgery and intravaginal radiation. Stage I was considered high risk if the tumor was of high grade or exhibited deep myometrial invasion. Vault radiation was delivered with a remote afterloading technique to a point .5 cm from the surface of the applicator; a total dose of 21 Gy was delivered in three fractions spaced two weeks apart over four elapsed weeks. With this regimen, the mucosal surface received a total equivalent dose of 40 Gy. These treatments were given on an outpatient basis without the need for any sedation or analgesics. All patients, regardless of stage, grade, or depth of myometrial invasion received adjuvant post-operative vaginal radiation. The minimum follow-up was 5 years, with a median follow-up of 8.5 years. The overall pelvic and/or vaginal recurrence rate was 2.7%. The incidence of vaginal complications was 3.7%. It appears that the remote afterloading treatment (RAT) for vaginal radiation is a very cost-effective therapeutic alternative, which produces minimal early or late complications and gives complete protection from radiation exposure to the medical staff. The advantages of a remote afterloading technique in delivering vaginal vault radiation in endometrial cancer are discussed in this paper.     

Neo-adjuvant therapy in childhood osteogenic sarcoma: a pilot study of selective postoperative chemotherapy based on response to preoperative high-dose methotrexate

"Neo-adjuvant therapy" with preoperative high-dose methotrexate (HD-MTX) and CF rescue therapy was investigated in four children with osteogenic sarcoma. Immediately after the diagnosis of osteogenic sarcoma from biopsy, the patients were treated with three to five courses of weekly HD-MTX (300 mg/kg) with CF rescue. Three patients had en bloc tumor resection and one patient underwent disarticulation of the hip joint after the pre-operative HD-MTX. The effect of HD-MTX was evaluated on the basis of pathological changes between the specimen of the primary tumor taken at biopsy and that during surgery. Two out of four patients showed marked tumor cell reduction (greater than 50%) of the specimen upon surgery. Two patients who responded to the preoperative HD-MTX were further treated with HD-MTX on a post-operative adjuvant therapy basis for 18 months. Both of these patients survived with no evidence of disease for 35.6+ and 20.9+ months. Two patients who responded poorly to HD-MTX were treated with a multi-drug postoperative adjuvant therapy including cis-platinum, adriamycin, cyclophosphamide, actinomycin D, and bleomycin. One patient had a solitary lung metastasis at 12.2 months after amputation. Wedge resection of the metastatic tumor was performed and adjuvant therapy with cis-platimum has been given for 20 months. He has remained with no evidence of disease for more than 30 months. Another patient has been receiving multi-drug neo-adjuvant therapy without any evidence of disease for 11.9 months after surgery. These data suggest that neo-adjuvant chemotherapy based on the response to preoperative HD-MTX is more useful for increasing the cure rate of childhood osteogenic sarcoma.