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Biomedical subjects

A K Murthy

Publications and source records attributed to A K Murthy.

At least 19 recordsLinked to original sources
PubMed1997

Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer: 8-year analysis of results.

BACKGROUND: The purpose of this study was to analyze long-term follow-up of a single institution's experience with a regimen of concomitant cisplatin/fluorouracil (5-FU) infusion and radiation given every other week. This analysis was stimulated by results of a randomized trial showing superiority for this regimen over induction cisplatin/5-FU chemotherapy followed by radiotherapy, especially in regional disease control. METHODS: All patients with stage III/IV disease who were referred by surgeons for nonoperative therapy and had a follow-up of at least 2 years were included. Concomitant chemoradiotherapy was administered days 1-5 of a 2-week treatment cycle, for a total of 7 cycles, with cisplatin 60 mg/m2 day 1, 5-FU 800 mg/m2 given over 24 hours days 1-5, and radiation 2 Gy days 1-5. RESULTS: Seventy-eight patients with stage III (n = 16) or IV (n = 62) were treated and followed for a median of 8 years. Six patients died during treatment, of aspiration pneumonia, sudden death, gastrointestinal bleeding, and stroke. When assessed 6 weeks after the end of treatment, 45 patients (63%) had no clinical evidence of disease, whereas 27 (37%) still had some persistent abnormality. However, 17 of these "partial responders" have not recurred. In all, 24 patients (31%) have recurred or progressed, 13 at the primary site, 5 after 3 years. None of 16 stage III and 24 (39%) of 62 stage IV patients ever progressed. Tongue and glottic larynx did best, with only 1 of 22 patients ever failing (none locally). Supraglottic and oral cavity cancers other than tongue had the worst failure rates. Nineteen patients (24%) died of other causes (DOC), tumor-free. Patients who DOC correlated strongly with T stage (p < .002) but not with N stage or with AJC stage. The 5-year progression-free survival was 60% (confidence interval [CI] = 49% to 72%), and overall survival was 43% (CI = 33% to 56%). CONCLUSIONS: Disease control for this advanced head and neck cancer population was excellent. This regimen was especially effective in advanced tongue and glottic cancers and all stage III disease sites. Advanced supraglottic and hypopharynx cancers are problematic. These, and especially T4 lesions, are associated with high DOC rates, possibly in part related to swallowing malfunction. Nevertheless, the long-term survival without surgical intervention was high with this regimen.

Adult↗
PubMed1997

Integration of surgery in multimodality therapy for esophageal cancer.

BACKGROUND: While adding chemotherapy to radiation for the treatment of esophageal cancers has been shown to be beneficial, surgery usually follows treatment or is omitted. In either case, regional control remains problematic. The purpose of this study was to test the feasibility of using chemotherapy and radiation following surgery in the treatment of of esophageal cancer and to assess the impact of this approach on regional control and survival. PATIENTS AND METHODS: Twenty-five patients with esophageal cancer were treated in a phase I pilot protocol consisting of initial esophagectomy with gastroesophagostomy and subsequent combined chemotherapy and radiation. Chemotherapy consisted of cisplatin given on day 1 and 5-fluorouracil (FU) on days 1-5 by continuous infusion. Radiation therapy was administered in varying fractionation schedules of once or twice daily concomitantly with the chemotherapy. Treatment was repeated every other week for two to four cycles. Median follow-up was 42 months. RESULTS: Acute toxicities (mucositis and cytopenias) were common but not worse than grade 3. Higher doses of 50 Gy with 2 Gy b.i.d. hyperfractionation caused late complications in four of 10 patients, (two lethal). Control of local disease for all patients was excellent with only two known and two possible local recurrences (16%) but distant metastases were common (46%). Disease-free survival was 58 and 30% at 1 and 2 years, respectively. Survival was 58 and 32% at 1 and 2 years, respectively (median survival, 19 months). CONCLUSION: The local control rate and survival were better than those in our historical experience with cisplatin and 5-FU chemotherapy and radiation given prior to surgery. A dose-fractionation schedule of < 2 Gy up to a total of 50 Gy b.i.d. is recommended to avoid late adverse effects. The role of surgery will be defined by randomized studies. Better systemic therapy is needed to impact on systemic failure.

Adenocarcinoma↗
PubMed1995

Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence.

BACKGROUND: The impact of delaying irradiation to the intact breast for patients receiving chemotherapy for lymph node positive breast cancer is controversial. METHODS: From 1974 to 1989, 474 patients underwent lumpectomy and intact breast irradiation for early stage invasive breast cancer. Chemotherapy was administered to 84 patients (1 patient with bilateral breast cancer) because of positive axillary lymph nodes. Time from definitive breast surgery (lumpectomy or reexcision) to the initiation of breast irradiation was 21-314 days, with a median of 124 days. Forty-two patients began receiving radiation therapy before 120 days (early) and 42 more than 120 days after surgery (delayed). In the early group, cyclophosphamide/methotrexate/5-fluorouracil (CMF) was administered to 32 patients, doxorubicin, cyclophosphamide or cyclophosphamide, doxorubicin, 5-fluorouracil (AC or CAF) to 6 patients, and other regimens to 4 patients; in the delayed group, CMF was given to 29 patients, CAF to 12 patients, and L-PAM/5-fluorouracil to 1 patient. RESULTS: Median follow-up was 62 months. There was one breast recurrence in the early group, compared with six in the patients receiving delayed irradiation. The actuarial relapse rates for these groups at 5 years were 2% and 14%, respectively (P = 0.05). Survival and distant disease free survival were not significantly different between the two groups. CONCLUSIONS: Delays in the initiation of irradiation are associated with increased risk of relapse in the breast. When possible, the interval between definitive breast surgery (lumpectomy or reexcision) and the initiation of radiation therapy should be fewer than 120 days.

Actuarial Analysis↗
PubMed1995

Wolman's disease.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1994

Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy?

PURPOSE: Multicentric cancer is present in a large proportion of mastectomies performed as treatment of breast cancer; it has been considered a contraindication to breast conservation. METHODS AND MATERIALS: We reviewed the records of our patients with Stage I or II breast cancer treated with breast conserving surgery and radiation therapy over a 13-year period. Twenty-seven patients had two or more nodules of grossly visible cancer separated by histologically normal breast tissue. All patients had grossly negative margins of excision; however, four patients had microscopically positive margins. Nine patients had positive axillary nodes. All patients received radiation therapy to the breast postoperatively, with a median dose of 50.4 Gy in 28 fractions; 11 patients also received a boost dose of 6-20 Gy to the tumor bed. Eleven patients were given adjuvant chemotherapy and one patient was given adjuvant tamoxifen. RESULTS: With a median follow-up of 53 months, only one patient has relapsed in the breast (3.7%); that patient relapsed in multiple distant sites at the same time. Three patients have died of disseminated disease; the actuarial survival and disease-free survival rates at 4 years are 89%. CONCLUSION: Breast conservation may be considered for patients with multicentric breast cancer discovered at the time of histologic examination. For patients with multicentric disease detected prior to surgery, breast conserving therapy may be appropriate as long as: (1) all clinically and radiographically apparent abnormalities are removed, (2) clear margins of resection are achieved, and (3) there is no extensive intraductal component.

Adult↗
PubMed1994

Pilot study for the evaluation of simultaneous cisplatin/5-fluorouracil infusion and limited radiation therapy in regionally recurrent head and neck cancer (EST P-C385).

From 1981 to 1989, 21 patients with heavily pretreated head and neck cancers were retreated with combined chemotherapy (CT) and irradiation (RT). All patients had previously received radiation therapy with doses of 50-70 Gy. Metastatic disease to lungs and/or osseous sites occurred in 4 patients. Treatment consisted of simultaneous cisplatin, 5-fluorouracil, and external beam radiation therapy, with planned doses of 20 to 70 Gy. The RT+CT was given over 5 consecutive days every 2 weeks. Four patients did not complete treatment due to toxicity (2 patients) or disease progression (2 patients). All patients developed grade 2-3 mucositis. Because of toxicity, 11 patients required treatment delays of 1 to 3 weeks. Clinically complete responses were noted in 10 patients (48%), with partial responses occurring in 5 patients (24%). Of the 21 patients, 18 have died: 13 had local and/or regional recurrence, 2 died of treatment toxicity and 3 died of intercurrent disease. Median time to progression was 5 months (range: 1-15 months). Three patients remain alive with no evidence of disease at 44, 86, and 88 months after retreatment.

Aged↗
PubMed1994

Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer.

PURPOSE: To compare two published schedules of cisplatin plus fluorouracil (5-FU) infusion and radiation as either sequential or concomitant treatment for toxicity and efficacy in patients with unresectable head and neck cancer. PATIENTS AND METHODS: This was a randomized trial between cisplatin 100 mg/m2 over 15 minutes on day 1 plus 5-FU 1.0 g/m2 by continuous infusion on days 1 to 5, repeated every 3 weeks for three cycles, followed by 70 Gy of radiation in 7 to 8 weeks, versus cisplatin 60 mg/m2 over 15 minutes on day 1 plus 5-FU 800 mg/m2 by continuous infusion on days 1 to 5 plus radiation 2 Gy on days 1 to 5, repeated every other week for seven cycles. Unresectable head and neck squamous cancer patients not previously treated with radiation or chemotherapy and with a performance status of 0 to 2 were stratified by tumor (T) and node (N) groupings and performance status and randomized. RESULTS: Two hundred fifteen patients were entered and 214 analyzed, 107 on each arm. After all treatment, overall response rates were different (P = .003), with similar complete response rates, but more partial responses and fewer patients with no change or progression with concomitant treatment. Cox regression analysis for progression-free survival identified concomitant treatment (P = .003), Radiation Therapy Oncology Group (RTOG) stage III grouping (P < .0001), performance status (P = .0002), concomitant treatment (P = .003), and treating institution (P = .006) as significant. The sequential and concomitant treatments showed similar distant failure patterns (10% and 7%, respectively), but divergent regional failure rates (55% and 39%). Severe and worse toxic events were similar between the treatment programs, but radiation-induced mucositis combined with cisplatin-induced water-losing nephropathy, in the concomitant arm only, demanded more supportive care. Survival duration was similar between the treatment arms, but significantly more patients in the sequential arm died of their cancer (P = .011). CONCLUSION: Concomitant treatment offered improved disease control, predominantly of regional disease, but benefit was dependent on the experience of the treating institution. Translation of this benefit into improved survival is not yet evident, with an excess of deaths from other causes in the concomitant arm.

Adult↗
PubMed1993

Long-term results of curative irradiation in pathologically staged IA and IIA Hodgkin disease.

One hundred seventy-six patients with pathologically staged IA and IIA Hodgkin disease (HD) treated with irradiation alone were evaluated for long-term survival and freedom from relapse (FFR). Most of the patients received treatment to mantle and paraaortic fields; chemotherapy was not given except as salvage therapy. For pathologically staged IA disease, the 5-, 10-, and 15-year survival rates were 94%; the corresponding FFR rates were 96%, 93%, and 93%. For pathologically staged IIA disease, respective survival rates were 93%, 89%, and 80%, with FFR rates of 86%, 84%, and 84%. Twenty-one patients (12%) had relapse of HD; salvage therapy was successful in 11 of these patients. Pelvic recurrence was uncommon (three of 176 cases [2%]). No patient developed leukemia, and only two patients developed second malignancies (lung cancer in both cases). The authors conclude that radiation therapy is effective in treatment of early-stage HD.

Adolescent↗
PubMed1993

Endodermal sinus tumor: report of 12 cases.

Twelve cases of endodermal sinus tumor were reviewed. There were 10 females and 2 males with a median age at presentation of 3 years. The primary site was sacrococcygeal in 4 patients, vaginal in 3, retroperitoneal in 2, and testicular, ovarian and left chest wall in one each. The diagnosis rested on histopathological examination and elevation of serum alfa feto protein levels (median 46,200 ng/ml). Two patients had Stage I disease, 9 had Stage III and one had Stage IV disease. Patients were managed by surgery and chemotherapy (BVP regime). All patients on BVP (even those lost at later stages), had achieved clinical remission with the first cycle of treatment.

Child↗
PubMed1991

Concomitant chemotherapy and split-course radiation for cure and preservation of speech and swallowing in head and neck cancer.

To assess the ability of simultaneous cisplatin, 5-Fluorouracil, and radiation to substitute for surgery and radiation in advanced head and neck cancer, we have retrospectively selected from our phase II study a subgroup of 29 patients having primary disease requiring either more than a hemiglossectomy or a laryngectomy for control. Patients included 22 with stage IV and 7 with stage III disease, 12 tongue, 10 hypopharynx, and 7 larynx primaries. The treatment consisted of concurrent cisplatin, 5-Fluorouracil, and split-course radiation every other week for a total of 7 cycles within 13 weeks. With a median follow-up of 5 years, 86% of patients had preservation of speech and/or swallowing function. Median survival was 45 months, with 14 (48%) patients currently alive and disease free, 11 (38%) dead from their cancer, and 4 (14%) dead of other causes. The overall failure rate was 38%. Advanced-stage presence of N3 nodal disease and fewer than 7 cycles of chemotherapy received were significantly associated with increasing failure rates. This program of concomitant cisplatin, 5-Fluorouracil, and radiation produced control rates quite competitive with surgery and radiation and is appropriate for definitive testing in a randomized trial.

Adult↗
PubMed1991

Peripheral nerve sheath tumours: an ultrastructural study of 30 cases.

This report deals with the ultrastructural observations of 30 peripheral nerve sheath tumours [PNST], which include 25 schwannomas of acoustic nerve, one schwannoma of cauda equina, one neurofibroma from a case of Von Recklinghausen's disease, one pigmented neurofibroma of spinal nerve root and a malignant schwannoma of frontal region. Interdigitating slender cytoplasmic processes covered with a continuous layer of basal lamina constitute the single most important ultrastructural attribute of Schwann cells. Myelin formation was encountered in the cell processes of four out of 25 acoustic schwannomas. In four cases Microtubular arrays identical to that in an axon were seen in Schwann cells. These two observations require further support by additional cases of PNST studies by electron microscopy. The neurofibroma consisted only of Schwann cells and no ultrastructurally identifiable perineurial cells or fibroblasts were detected. The cells in the pigmented neurofibroma revealed submicroscopic features of both Schwann cell and melanocyte, indicating their common ancestry. A unique case of malignant schwannoma arising from frontal meninges is illustrated and it is emphasized that electron microscopy is mandatory for a correct histogenetic diagnosis of malignant tumours which occur at unexpected anatomical sites.

Adult↗
PubMed1990

Technique for breast irradiation using custom blocks conforming to the chest wall contour.

A technique for the treatment of the breast and regional nodes is presented. The technique involves the use of tangential fields to treat the breast and chest wall. Customized blocks which conform to the slope of the chest wall are made for each tangent field. Simulation and treatment with this technique requires no special equipment. The setup is simple and quick. A three-field technique is also described using the custom half-beam blocks; this technique avoids the use of tangential field corner blocks, thus simplifying simulation and treatment.

Breast↗
PubMed1990

Retrospective analysis of hyperthermia for use in the palliative treatment of cancer: a multi-modality evaluation.

Forty-two patients with local or superficial metastatic or recurrent malignant tumors were treated in a non-randomized Phase I/II study to assess the tumoricidal effects of heat combined with radiation and/or chemotherapy. Radiation doses administered averaged 3130 +/- 350 cGy; chemotherapeutic agents employed included bleomycin, mitomycin-C, adriamycin, and cis-platin, heat was induced by radiative or interstitial microwave applicators operating at frequencies ranging from 95 to 900 MHz. Forty-one of the forty-two patients were evaluated for initial therapeutic effects yielding the following response distributions: local hyperthermia with radiation--42% complete response (CR), 44% partial response (PR), and 15% no response (NR); local hyperthermia with chemotherapy--0% CR, 50% PR and 50% NR. Long-term response duration was evaluated for local hyperthermia with radiation, yielding mean time to recurrence of 9.4 months for CR's and mean time to progression of 3.4 months for PR's. In retrospective analysis, we examined the correlations of previously established response-predictor variables of tumor volume and minimum thermal dose with both initial and long-term response rates. Initial complete response rates were correlated directly with non-site-specific minimum thermal dose, varied inversely with tumor volume and exhibited a positive correlation for a limited histologic type/treatment site combination. Surprisingly, long-term response did not correlate either with tumor volume or thermal dose. The frequency of thermally induced complications, which did not correlate with any measured thermal parameters, was found to be 42%, expressed on a per-patient basis.

Adult↗
PubMed1989

Spontaneous vesicle formation in aqueous mixtures of single-tailed surfactants.

Spontaneous, single-walled, equilibrium vesicles can be prepared from aqueous mixtures of simple, commercially available, single-tailed cationic and anionic surfactants. Vesicle size, surface charge, or permeability can be readily adjusted by varying the ratio of anionic to cationic surfactant. Vesicle formation apparently results from the production of anion-cation surfactant pairs that then act as double-tailed zwitterionic surfactants. These vesicles are quite stable in comparison to conventional vesicles prepared by mechanical disruption of insoluble liquid crystalline dispersions.

Benzenesulfonates↗
PubMed1989

Combined simultaneous cisplatin/fluorouracil chemotherapy and split course radiation in head and neck cancer.

Fifty-three patients with stage III (eight patients, 15%), stage IV (36 patients, 68%), or recurrent disease (nine patients, 17%) entered a study of simultaneous cisplatin, 60 mg/m2 day 1, fluorouracil (5-FU) infusion, 800 mg/m2 days 1 to 5, and radiation, 2 Gy days 1 to 5, every other week for a total of seven cycles (70 Gy in 13 weeks). Patient acceptance was high, with only two patients (4%) refusing to complete therapy. The median actual dose delivered was 88% of the planned dose for cisplatin, 78% for 5-FU, and 70 Gy for radiation. Weight loss of 10% or more and severe mucositis were the most common side effects (53% and 48% incidence, respectively). All patients were followed at least 1 year (median, 51 months). While the complete response rate (55%) seemed no better than that reported in other series, freedom of progression of regional disease (73%), and the survival of all patients (median, 37 months) were substantially improved. Only 33% of partial responders have failed regionally, while 15% of complete responders have failed regionally (P greater than .10), which indicates that clinical assessment of response was unreliable. Stage, the presence of N3 disease, and delivery of less than the median actual dose received of 5-FU (but not cisplatin) were significantly associated with failure. This regimen is feasible and tolerable in this difficult patient population. It generally requires no special forced feeding techniques. Survival results from this limited institution study appear better than those using sequential multimodality therapies. With such favorable regional control, this approach may offer an alternative in the future to radical surgery and radiation in resectable disease. More definitive evaluation seems warranted.

Actuarial Analysis↗
PubMed1988

Concomitant therapy with infusion of cisplatin and 5-fluorouracil plus radiation in stage III non-small cell lung cancer.

Based on our experience with head and neck cancer, we have developed an every-other-week, split-course schedule for giving combined cisplatin and 5-fluorouracil infusion and radiation to patients with regionally advanced non-small cell lung cancer for a limited number of cycles prior to planned resection. Sixty-four patients having stage III disease without distant metastases were treated with 4 cycles of combined chemotherapy and radiation to 40 Gy and were offered surgical resection. Thirty-nine patients (61%) underwent surgery. Nine had no residual cancer. No correlation was noted between clinical and histologic responses in the surgery group, but histologic response correlated with subsequent outcome. Survival was 58% at 1 year, 33% at 2 years, and 22% at 3 years. Although encouraging, the overall dismal prognosis of this disease has led us to pursue further improvements in protocol design prior to phase III testing of this concept. To this end, etoposide has been added to the above regimen, extending the cycles from every other week to every third week.

Antineoplastic Combined Chemotherapy Protocols↗