Preirradiation Chemotherapy Research Articles

Ependymomas in children.

Ependymomas originate throughout the central nervous system (CNS), representing 10-12% of CNS tumors in children. The majority occur in children less than 5 years of age. Tumors occur most often in the 4th ventricular region. Current controversies regarding ependymomas include histologic categorization or 'differentiation'. It is estimated that approximately 25% of childhood tumors are appropriately categorized as anaplastic or 'high-grade' lesions. Surgical resection is curative for tumors originating in the cauda equina; recent data suggest that surgery alone has achieved disease control in 75% of intramedullary tumors. For intracranial ependymomas, postoperative irradiation has been shown to improve survival in series dating from the 1960-1980 era. Debate regarding the necessary volume for radiation therapy (i.e. local treatment or craniospinal irradiation) centers on the reported rate of neuraxis seeding. An overall incidence of 12% has been documented in the literature, with clinico-histologic correlation suggesting that anaplastic or high-grade infratentorial ependymomas are associated with the highest frequency of subarachnoid spread. Recent reports of chemotherapy show response to several single agents, with no clear documentation that adjuvant chemotherapy has improved survival to date. Current studies utilizing preirradiation chemotherapy address tumor response and ultimate control in a sequence of surgery, chemotherapy, and irradiation primarily in very young children or those with anaplastic or high-grade tumors.

Pre-irradiation chemotherapy in malignant brain tumor: A phase II trial

Pre-irradiation chemotherapy in malignant brain tumor: A phase II trial

Palliative radiotherapy for ovarian cancer

Large single-fraction irradiation is effective palliation for advanced ovarian cancer. It has an acceptable complication rate and requires only a limited number of visits (i.e., one treatment per 4-week course) to administer. Forty-two patients received single or multiple fractions of (three maximum) 10 Gray (Gy) to the pelvis. Most patients had advanced disease, 71.4% had Stage III or IV and 90.5% Grade 2 or 3 at the time of diagnosis. Forty patients had received preirradiation chemotherapy. Tumor size before and after radiotherapy was evaluable in 34 patients and decreased in 25. Bleeding decreased or stopped in 15 of 21 patients, and pain lessened or ceased in 11 of 20 patients. Thirteen patients had surgical procedures performed after irradiation therapy. Ten had gastrointestinal procedures, and in six radiation injury was believed to be the main contributor to complication. Hemorrhagic cystitis or proctitis occurred 6 to 18 months after irradiation in four patients. Three of these four patients received three 10 Gy fractions. The safest and most efficient dose may be one or two fractions, since three 10 Gy fractions may not increase palliation.

Pre-irradiation chemotherapy of malignant brain tumor

Pre-irradiation chemotherapy of malignant brain tumor

Testicular seminoma: Analysis of treatment and failure for stage II disease

Seventy-three patients with seminoma testis stage II have been retrospectively analyzed with regard to prognostic factors and value of prophylactic mediastinal irradiation and chemotherapy. Although survival differences were seen between stage IIa, IIb and IIc, these were not statistically significant. Neither was there a significant difference between IIc patients with tumors greater than 10 cm and less than 10 cm in diameter. The incidence of HCG-producing seminomas in the present series was 16%. No significant difference in survival nor relapse rate was found between HCG-producing and HCG-non-producing seminomas. Prophylactic mediastinal irradiation did not influence the survival nor the relapse rate and may therefore be omitted. In the present series there was no significant improvement neither in relapse rate nor survival in patients receiving pre-irradiation chemotherapy. However, the total number of patients is small and optimal pre-irradiation chemotherapy still have to be defined.

Preirradiation chemotherapy for advanced head and neck carcinomas.

Twenty-six patients with locally advanced squamous cell carcinoma of the head and neck region were treated with combination chemotherapy (cisplatin, bleomycin sulfate, and vincristine sulfate) prior to radiotherapy (RT). The chemotherapy produced a 65% major response rate, all partial responses. Significant hematologic toxic effects occurred in only two patients and severe renal toxic effects were not seen. Concurrently, 20 additional patients with locally advanced cancers were treated with high-dose RT along. Weight loss at the completion of RT and normal tissue reactions were similar in both groups. Complete tumor resolution occurred in 45% of RT-alone patients and 42% of patients completing combined-modality therapy. No difference in recurrence-free survival was seen. Despite minimal additional morbidity and a high response rate, this preirradiation chemotherapy regimen demonstrated no major impact on complete response rate or on long-term recurrence-free survival.

Combined radiation and drugs: The effect of intra-arterial chemotherapy followed by radiotherapy in head and neck cancer

This study was designed to ascertain whether a prior reduction of tumor size by drugs could affect the final outcome of tumors treated with radiation. 142 patients with head and neck cancer (oropharynx, maxillary antrum and intra-oral) were randomized for the study. In 72 cases, irradiation was preceded by a continuous intra-arterial infusion of 3-5 mg/day methotrexate to a total dose of 90-120 mg; the other 70 patients were treated with radiotherapy alone. Chemotherapy, given prior to radiotherapy, caused a shift in the tumor stage (i.e. a reduction in tumor size) in more than one third of the cases. The overall 5-year survival was 43% in the combined treatment group and 25% in the group treated with radiation alone (statistical difference: p less than .05). However, when analysed separately the difference was statistically significant only in oral cavity tumors (5-year survival of 54% in the combined modality group vs. 27% in the control group), although local control rates after both single and combined modalities were not statistically different from those of oropharynx and maxillary antrum tumors. In these last lesions, however, the dissemination of disease was more frequent; therefore, the lack of improvement of cure rate with the combined modality in these cases seems to be related to both the higher tendency of these tumors to disseminate and the low effectiveness of intra-arterial chemotherapy in controlling distant metastases. Mild and transient local and systemic toxicities were observed during chemotherapy infusion, but no radiosensitising effect on normal skin and mucosa was seen during radiotherapy in patients who had received pre-irradiation chemotherapy.

Primary radiation therapy in the treatment of anal carcinoma

From 1966 to 1981, 47 patients with a diagnosis of anal carcinoma were irradiated. This group was composed of 23 males and 24 females, with age ranging from 38–84 years (average 64.4 years). The average age of the males was eight years less than the females. Of the 47 patients, 39 had an intact anal canal following biopsy and were treated with curative intent. Thirty-one of these 39 had no evidence of nodal metastasis (N 0) and eight had groin, pelvic and/or para-aortic nodal disease. Only three patients were treated with pre-irradiation chemotherapy; all had locally advanced disease. Five patients were treated preoperatively and 34 were treated definitively with cancericidal doses of irradiation. Acute radiation reactions requiring a rest-break were noted in 28 % of patients, but all were managed as outpatients without untoward chronic sequelae. Chronic complications were noted in 13 patients, including two patients who required colostomy for severe anal stenosis and two who required A-P resection for large painful ulcers. Two of these four patients had received part of their treatment with an interstitial implant and one had an excessively high dose of perineal irradiation. Twenty-eight of 35 patients (80%) treated with irradiation alone have remained locally controlled without further treatment. An additional four have been salvaged by surgery. Only three patients had interstitial implants as part of their treatment course. Actuarial survival at five years for the N 0 patients and the group as a whole are 95.6 and 79.3%, respectively. It is concluded that external beam irradiation alone, properly fractionated to cancericidal doses, can control anal carcinoma with acceptable morbidity rates and without the use of either chemotherapy or interstitial implants in most cases. There is also a strong correlation suggesting that anal intercourse and male homosexuality play a significant role in the etiology of this disease.

High-dose methotrexate and Adriamycin in osteogenic sarcoma

From 1975 through 1979, 25 patients with osteosarcoma received therapy with vineristine, high-dose methotrexate, citrovorum factor, and Adriamycin. Five patients had metastases prior to receiving chemotherapy, and 11 of the remaining 20 nonmetastatic patients received preoperative or preirradiation chemotherapy. Chemotherapy caused objective tumor regression in 1 of 5 patients with metastases and 1 of 11 with measurable primaries. All five patients with metastatic disease died 7-16 months from diagnosis. Of the 20 nonmetastatic patients, 4 did not have primary amputations: all died. Of 16 patients with primary amputations, 6 are alive relapse-free 24-86 months from diagnosis, and 10 are dead. The actuarial survival of 36% is not statistically different from that of historical control groups or from that of concurrent control groups treated with surgery alone. However, because most adjuvant chemotherapy studies have involved few patients, 36% survival is not statistically different from the 50-70+% survival reported in previous studies. Our data fail to demonstrate that the adjuvant chemotherapy has improved the survival rate of children with osteosarcoma. We support a randomized, controlled comparison of adjuvant chemotherapy and aggressive surgical resection.

High-dose methotrexate and Adriamycin in osteogenic sarcoma

From 1975 through 1979, 25 patients with osteosarcoma received therapy with vincristine, high-dose methotrexate, citrovorum factor, and Adriamycin. Five patients had metastases prior to receiving chemotherapy, and 11 of the remaining 20 nonmetastatic patients received preoperative or preirradiation chemotherapy. Chemotherapy caused objective tumor regression in 1 of 5 patients with metastases and 1 of 11 with measurable primaries. All five patients with metastatic disease died 7-16 months from diagnosis. Of the 20 nonmetastatic patients, 4 did not have primary amputations: all died. Of 16 patients with primary amputations, 6 are alive relapse-free 24-86 months from diagnosis, and 10 are dead. The actuarial survival of 36% is not statistically different from that of historical control groups or from that of concurrent control groups treated with surgery alone. However, because most adjuvant chemotherapy studies have involved few patients, 36% survival is not statistically different from the 50-70+% survival reported in previous studies. Our data fail to demonstrate that the adjuvant chemotherapy has improved the survival rate of children with osteosarcoma. We support a randomized, controlled comparison of adjuvant chemotherapy and aggressive surgical resection.

A new fractionation technique of total abdominal irradiation in ovarian cancer

Postoperative total abdominal irradiation was accomplished in 22 patients operated on for ovarian carcinoma, by employing a particular chess board-like technique of irradiation. A total midplane dose of 4000 rad in 10 fractions and 4800 rad in 12 fractions in an overall treatment time of 45 days is administered to the upper and middle abdomen and to the pelvis, respectively, with mild side effects. The good tolerance noticed in all our cases seems to be ascribed to the particular fractionation of the volume to be irradiated and of the dose, which takes into account the reproductive patterns of the normal dynamically proliferative intestinal cells and the slowly or nonproliferating cancer or connective tissue cells. Bone marrow depletion was the main reason for delaying or discontinuing the treatment. Preirradiation chemotherapy should be avoided in order to safely complete radiation therapy in the foreseen period of time.

A Comparative Treatment Results of Oesophageal Squamous Cell Carcinoma by Neoadjuvant Chemotherapy followed by Radiotherapy versus Radiotherapy Alone

Background: Studies suggest that neoadjuvant chemotherapy prior to radiotherapy results in improved response and survival in large primary lesion. This study aimed to evaluate the role of neoadjuvant chemotherapy prior to radiotherapy in patients with localized oesophageal cancer. Method: In this randomized controlled study 60 selected cases of oesophageal squamous cell carcinoma were randomized to Arm-A & Arm-B. Patients assigned to combination therapies(Arm- A) received two cycles (4 weekly) of injectable 5- fluorouracil(400mg/m2/day for five days ) and mitomicin C (7mg/ m2 on D1) as neoadjuvant chemotherapy prior to radiotherapy(44GY in 22 fractions). Patients of Arm-B received radiotherapy alone as in arm-A. Treatment responses were compared following completion of treatment at six and 12 weeks. Complete response was defined as no difficulty in swallowing and no visible growth in follow-up barium swallow X-Ray. Partial response was defined as difficulty in swallowing semisolids but not liquids and persistence of residual growth in barium swallow X-Ray. Results: The study initially enrolled 68 patients but eight patients dropped out. Complete response occurred in 66.6% (20) patients who received combination therapies (n=30), where as in 40% (12) patients who received radiotherapy alone (P= < 0.05). Partial response occurred in 33.33% patients assigned to have pre-irradiation chemotherapy and in 60% patients having radiotherapy alone. Toxicities like dysphagia, anorexia, vomiting was more in combination therapy group, but it was acceptable. Conclusion: Neoadjuvant chemotherapy followed by radiation therapy demonstrated better response than radiation alone at the expense of toxicity in patients with localized oesophageal cancer. Â DOI = 10.3329/jom.v8i2.1409 J MEDICINE 2007; 8 : 60-63

Mechanisms of action of radiotherapy and chemotherapeutic adjuvants. A review.

A review of the rationale for application of combined radiation and chemotherapy in the treatment of certain malignant tumors has been presented. The mechanisms of action of ionizing radiations and many of the commonly employed chemotherapeutic agents are intimately related to the nucleic acid metabolism of proliferating cells. Modification of the DNA-molecule by certain chemotherapeutic agents results in sensitization of the cell to subsequent irradiation. Reduction in the total number of malignant cells by preirradiation chemotherapy facilitates subsequent radiotherapy of advanced tumors. Certain chemotherapeutic antitumor agents exert a beneficial effect by restraining the growth of distant metastases which often escape clinical detection.