Combined external beam radiotherapy and vaginal brachytherapy versus vaginal brachytherapy in stage I, intermediate- and high-risk cases of endometrium carcinoma.

PURPOSE: Randomized trials on the effect of external beam radiotherapy (EBRT) with or without vaginal brachytherapy (VBT) for endometrial carcinoma are very few. In view of this, the current study was conducted with the hypothesizes: whether the escalated dose of 26 Gy (VBT alone) in comparison with various major international trials (PORTEC-2) has any difference in rates of disease-free and overall survival with fewer adverse effects in low resource setting like India. MATERIAL AND METHODS: An open-labeled, non-inferiority, randomized control trial was undertaken at a regional cancer center among patients with stage IA or IB high-intermediate risk endometrial carcinoma. A total of 50 patients were divided equally among two arms of combined EBRT with VBT (arm I) and VBT alone (arm II). A dose of 50-50.4 Gy in 25-28 fractions of EBRT with 2 fractions of VBT 6.5 Gy each were delivered to patients in arm I and 4 fractions of VBT 6.5 Gy each to patients in arm II, and were followed up for 60 months. RESULTS: During the median follow-up of 36.5 months, two patients developed loco-regional recurrence in arm II, three (arm II), and one (arm I) developed distant metastasis. The 5-year survival rates for arms I and II were 96.0% vs. 92.0% overall, and 88.0% vs. 84.0% disease-free, respectively, and were not found to be statistically significantly different. Dermatological, gastro-intestinal toxicities, and cystitis were lower in the VBT group compared to combined group. CONCLUSIONS: VBT alone is as effective as EBRT+VBT in ensuring loco-regional control and achieving comparable survival rates, with fewer toxic effects for patients with stage I intermediate- and high-risk endometrial carcinoma. The dose escalation did not make a difference in the survival rates and was like in the other major trials (PORTEC-2).

A study of serum zinc, selenium and copper levels in carcinoma of esophagus patients.

The association of serum trace elements like selenium, zinc and copper has been found in different types of cancer. This study was conducted to see the serum level of these three trace elements in cancer esophagus patients. Biopsy confirmed cancer esophagus, 24 patients (12 males, 12 females, mean age 54.5±11.65 year with 23 healthy subjects (16 males, 7 females, mean age 44 ±13.82 years) were included in this study. Both control and study group patients were of same socio-economic status and dietary habits. Serum zinc and copper level were estimated using standard absorption spectrometer technique and serum selenium by Hydride generation method.We observed significant low serum levels of zinc and selenium while high level of serum copper in carcinoma esophagus patients, as compared with normal healthy controls. This shows an association of serum selenium zinc and copper with cancer esophagus.

Role of pretherapeutic biomarkers in predicting postoperative radiotherapy response in patients with advanced squamous cell carcinoma.

PURPOSE: To assess the role of biomarker levels in predicting radiotherapy (RT) response in patients with squamous cell carcinoma of buccal mucosa treated with postoperative RT. MATERIALS AND METHODS: Thirty-one patients with squamous cell carcinoma of buccal mucosa who received postoperative RT were enrolled for the study. Glutathione S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase activity were analysed from primary tumour and adjacent normal mucosa of the same patients before RT. p53 and p21ras were localized immunohistochemically. RESULTS: Enzyme activation was predicted by comparing the levels of these enzymes in tumour and adjacent normal mucosa. Deactivation of GST, activation of GR, SOD and catalase were associated with poor response to RT. p53 immunoreactivity was associated with failure to respond to RT. CONCLUSIONS: These markers may be useful in predicting treatment outcome in patients receiving postoperative RT, although this conclusion requires confirmation in a larger group of patients.

Surgery versus surgery and postoperative radiotherapy in squamous cell carcinoma of the buccal mucosa: a comparative study.

BACKGROUND: The efficacy of postoperative radiotherapy for squamous cell carcinoma of the buccal mucosa was evaluated. METHODS: One hundred seventy-six patients treated between 1989 and 1993 were analyzed. One hundred fifteen patients were treated with surgery alone (Group 1), and 61 patients were treated with a combination of surgery and postoperative radiotherapy (Group 2). RESULTS: Actuarial 3-year locoregional control in Groups 1 and 2 was 11% and 48% for patients with stage III + IV cancer (P = .001) and 71% and 75% for patients with stage I + II cancer (P = .74), respectively. On multivariate analysis for locoregional failure, surgical margin, bone invasion, high grade, and node involvement were significant factors in Group 1, whereas in Group 2 only tumor thickness was a significant factor. For local failure, margin, bone invasion, and stage in Group 1 and tumor thickness in Group 2 appeared as significant factors. For nodal failure, clinical nodal (cl N0 vs. N+) stage and grade in Group 1 and pathologic nodal stage (pN0 + 1 vs. pN2) in Group 2 were observed as significant factors. On subset analysis, postoperative radiotherapy was observed to have a significant advantage for surgical margins of 2 mm or less in both early pT (T1 + T2) (P = .019) and late pT (T3 + T4) (P = .016) stages. The local failure rate was higher if the time between surgery and radiotherapy was greater than 30 days. CONCLUSIONS: Postoperative radiotherapy was effective in decreasing locoregional failure in patients with close surgical margins, tumor thicker than 10 mm, high-grade tumors, positive node, and bone invasion. The effect of interval between surgery and postoperative radiotherapy on local failure was margin-dependent.

Inoperable non-small cell lung cancer: palliative radiotherapy with two weekly fractions.

Thirty seven cases (30 males; 7 females) of advanced non-small cell lung cancer were treated with short course of palliative radiotherapy. All the patients were inoperable. Their main symptoms were related to primary intrathoracic disease and poor performance status. Radiotherapy was delivered to a total dose of 17 Gy in two fractions one week apart. Ninety percent of the patients had cough, 50% complained of haemoptysis, 45% chest pain and 30% breathlessness. Palliation of main symptoms was achieved in majority of the patients, more than 90% in haemoptysis, 60% in cough, 70% in chest pain and 50% in breathlessness. Mean duration of palliation was four months and performance status improved in 60% of the patients. Short course radiotherapy of 17 Gy in two weekly fractions is recommended in patients with advanced non-small cell lung cancer (NSCLC) having poor performance status.

Rectosigmoid complications of radiotherapy in stage 3B carcinoma of the cervix.

A retrospective analysis of 165 patients with Stage 3 B carcinoma of the cervix treated with radiotherapy alone was done; 120 patients were treated with a combination of external radiotherapy and intracavitary treatment while 45 patients received external radiotherapy only. Early rectosigmoid reactions were seen in 65% of cases with Grade 1, 2 and 3 reactions in 40%, 20% and 5% of cases respectively. Late rectosigmoid sequelae were observed in 25 patients (16%) with moderate complications in 5%. Severe rectal complications were seen in 2 women only. Rectosigmoid complications are the most common sequelae of pelvic irradiation and seen more in advanced stages where a greater dose is given by external radiotherapy. The role of rectal dosimetry is equivocal if proper precautions are taken during intracavitary treatment.

Post orchiectomy management in stage II testicular seminoma.

Twenty eight patients with stage II A and twenty patients with stage II B testicular seminoma were treated at this institute between January 1982 and December 1988. The three year crude survival observed in this retrospective analysis was 82% and 75% respectively. Post orchiectomy infradiaphragmatic radiotherapy was the mainstay of the treatment. In stage II A 4 patients were administered adjuvant chemotherapy as well. Prophylactic Mediastinal Irradiation (PMI) was not employed as a routine in this subgroup. Eight patients (28%) relapsed (Mediastinal Nodes--4, Pulmonary--3, Scrotal--1). In stage II B twelve patients were treated with primary abdominal radiotherapy and of them 4 were delivered PMI as well. Induction chemotherapy was administered in remaining 8 patients. Seven patients (35%) relapsed (Pulmonary-4, Mediastinal Nodes-3). Mediastinal recurrence was noted only in those who were treated with abdominal radiotherapy alone. Though salvage chemotherapy proved successful in 5 of the seven patients (70%) with nodal relapse, none of the patients with extranodal relapse responded to subsequent chemotherapy. For stage II A we recommend abdominal radiotherapy alone and for stage II B Induction chemotherapy is advised keeping radiotherapy reserved for residual mass. We do not advocate PMI as a routine in stage II testicular seminoma as no survival benefit is observed.

Carcinoma of the oesophagus: correlation of radiological appearance with response to radiotherapy.

In order to predict possibility of local control in carcinoma of the oesophagus by radiotherapy, the relationship between the x-ray findings before and after radiotherapy were analyzed in 55 irradiated cases. In the superficial or proliferative type on x-ray before treatment, local control was observed in 87% cases with dose of 40 Gy, whereas in the ulcerative or infiltrative type it was observed in 20% cases. Radiation response is remarkably good in proliferative and superficial lesions seen in oesophagogram.

Leiomyosarcoma of the ovary.

A diagnosis of leiomyosarcoma of ovary was made in a 60 year old female presenting with generalised weakness and abdominal lump. On clinical examination, a hard, big mass with some cystic areas was found occupying the pelvic cavity. Chest X-ray revealed presence of metastases. Deranged renal function and structure due to extrinsic pressure were evident on pyelography and USG. USG also suggested the ovarian origin of the mass. Fine needle aspiration biopsy was suggestive of leiomyosarcoma. Laparotomy was carried out for excision of tumor along with bilateral salpingo-oophorectomy and hysterectomy. Post-operatively renal functions normalized. A course of radiotherapy was given. At 6 months' follow-up, abdomino-pelvic sonography was normal but lung metastases were found to be enlarged. The patient was asked to follow up for chemotherapy but did not come. She died 18 months after treatment, as revealed through correspondence.

Post-orchiectomy management in stage I testicular seminoma: elective irradiation or surveillance?

Fifty-six patients with stage I testicular seminoma were treated at this institute between January 1982 and December 1988. Post-orchiectomy elective radiotherapy to ipsilateral iliac-inguinal and para-aortic lymph nodes was delivered in 54 cases. An overall 3 year survival rate of 96% was observed in this series. Four patients (7%) relapsed (one junctional recurrence in iliac node region, two mediastinal/hilar nodes and one skeletal metastasis). Salvage chemotherapy proved successful in two out of three cases with nodal relapse. No dose limiting acute or late radiation related complications were noticed. No definite correlation was found between the patients who relapsed and various known adverse prognostic factors. We recommend elective irradiation of the draining lymph nodes in stage I seminoma, particularly at centres where surveillance is not feasible.

Effect of optical isomers of gossypol on mammalian spermatozoa: an in vitro study.

Human, bull and monkey spermatozoa were treated with different optical isomers of gossypol in vitro. The spermatozoa (concentration 50 x 10(8)) were incubated with gossypol for 15, 30, 45 and 60 min. at 37 degrees C. The concentration of gossypol employed in the experiment was from 5-50 micrograms/ml. A marked inhibition in sperm motility was observed following gossypol treatment; levorotatory gossypol had more pronounced effect on sperm motility in comparison to dextrorotatory and racemic gossypol. Scanning electron microscope study revealed degenerative changes in the sperm head surface. Dextrorotatory gossypol, hitherto known to be non-effective in suppressing the fertility in vivo was found to be equally effective in inhibiting the motility and LDH-X activity of the spermatozoa. Both racemic and dextrorotatory gossypol inhibited fructolysis in bull spermatozoa. Our data suggest that whatever the mechanism of action of enantiomers of gossypol on sperm motility, fructolysis and LDH-X may be, it is evidently clear that dextrorotatory gossypol is equally active in inhibiting the sperm motility and enzyme active in vitro. The action of optical isomers of gossypol on spermatozoa in vitro, appears to be unrelated to the mechanism of orally administered gossypol.

Response of mice testis to gossypol acetic acid.

Male mice were administered gossypol (2.5, 5.0, 10.0 and 20.0 mg/kg body weight) by oral intubation, subcutaneous and intraperitoneal routes for 30 days. The drug treatment did not have any effect on body weight and organ weights. The motility of cauda epididymis and vas deferens spermatozoa was not affected by gossypol treatment nor there was any effect of gossypol on the histoarchitecture of the testis irrespective of the dose and route of administration. Maximum mortality was observed in mice when animals were given gossypol by intraperitoneal route.

Recovery of normal testis function and sperm motility after cessation of gossypol treatment in hamster.

The present investigations evaluate the reversibility of the effect of gossypol on the histoarchitecture of the hamster testis and the motility of the vas deferens spermatozoa. Adult male hamsters of proven fertility were treated orally with gossypol (10 mg/kg/day) for 13 weeks (group III). Another group of animals in the Group IV were given gossypol (10 mg/kg/day) for 13 weeks and were sacrificed 13 weeks after termination of the drug treatment. Animals in groups I and II were given vehicle and served as controls for groups III and IV respectively. To all the animals, gossypol or vehicle was administered by oral intubation. A marked reduction in the spermatozoa motility was observed in the animals of group III. In contrast, the motility of the spermatozoa in the animals of group IV (recovery phase) was in the normal range. A large number of seminiferous tubules were affected by gossypol treatment (group III); these tubules showed degeneration of germ cells, vacuolization and loosening of the germinal epithelium. In the quantitative analysis of the spermatogenic events, the ratio of resting spermatocyte/'A' type spermatogonia was not affected but the ratios of pachytene spermatocytes/resting spermatocytes and stage 19 spermatids/stage 7 spermatids decreased by 21%, 47% and 52% respectively. The tubular diameter and germinal height were decreased by 14% and 33% respectively. In group IV, hamsters were allowed to recover from the gossypol treatment. The seminiferous tubules exhibited normal histoarchitecture and the tubular diameter and germinal height recovered markedly. Recovery in different stages of spermatogenic cycle was evidently clear in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Early events in rat testis after gossypol administration.

Eighty male rats were grouped into 8 groups of 10 animals each. Animals in groups I-IV were given gossypol (40 mg/kg/day) for 7, 14, 21 and 28 days respectively. Animals of groups V-VIII served as respective controls for groups I-IV. Marked changes in the activities of ATPase and SDH were observed following drug treatment. Decrease in the activity of testis LDH was evident even after 7 days of drug treatment. Activities of B-galactosidase, Glucose-6-phosphatase and Fructose-1-6-diphosphatase were not affected by gossypol treatment. Glycogen contents in testis were not different from those of the controls. A significant decrease in the tubular diameter and germinal height of the seminiferous tubules was observed after 21 days of drug treatment. Quantitative analysis of spermatogenic elements revealed marked decrease in the ratios of resting spermatocyte. A type spermatogonia, pachytene spermatocyte/resting spermatocyte, and stage 19 spermatids/stage 7 spermatids after 7 days of drug treatment. A progressive decrease in the ratios of these cell types was observed as the duration of the drug treatment was extended. Liver enzymes (except SDH and LDH after 28 days of drug treatment) were not affected by gossypol treatment. Our data strongly suggest that degenerative changes in the testis start after one week of drug administration. The histological changes visible at light microscopy level start appearing after 14 days of drug treatment.