Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome and prognostic value of margin status

BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.     

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.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Recurrent pericarditis due to mesalamine hypersensitivity: a pediatric case report and review of the literature

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis. METHODS: Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26. 1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05). CONCLUSION: These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer.     

A novel zinc finger cDNA with a polymorphic pentanucleotide repeat (ATTTT)n maps on human chromosome 19p

PURPOSE: To evaluate the therapeutic effectiveness of a combined chemoradiotherapy program, followed by surgery in selected cases, in Stage III non-small cell lung cancer. METHODS AND MATERIALS: Between August 1988 and February 1990, 43 patients Staged IIIa-b (UICC 1987, 58% IIIb) have been treated with concomitant chemotherapy (cisplatin 15 mg/m2 and VP16 75 mg/m2, 5 days a week on week 1 and 5) and radiotherapy (40 Gy split course, 2 Gy/day on week 1, 2, 5, and 6), followed by attempted curative thoracotomy or more cycles of full dose chemotherapy with the same two drugs. RESULTS: Planned chemoradiotherapy has been given to 91% of patients; 13/43 patients have been operated, with 12 complete resections and three (7%) pathological complete responses. Toxicity was significant, with two postoperative deaths and two fatal radiation pneumonitis. Crude progression-free survival rate is 21% at 30 months, with nine patients (21%) alive and free from progression at follow-up times ranging from 31 to 49 months. Subset survival analysis showed a possibly greater therapeutic effect for non-squamous histology as compared to squamous carcinoma. CONCLUSION: These results are encouraging in a cohort of patients with quite advanced disease (58% Stage IIIb).     

The impact of do-not-resuscitate orders on nursing workload in an ICU

BACKGROUND: This study retrospectively examines our treatment choices and outcomes with patients diagnosed with squamous cell cancer of the floor of mouth. Because of our division's past strong surgical bias in the treatment of this disease, we have assessed the results of a patient population treated largely by surgical extirpation. This clinical information has been used to draw conclusions and formulate treatment paradigms for patients with floor of mouth cancer. METHODS: Four hundred fifty patients with the diagnosis of squamous cell carcinoma of the oral cavity received their primary treatment at Roswell Park Cancer Center (RPCI) from 1971 to 1991. Ninety-nine had disease originating in the floor of mouth and are the basis of this retrospective review. RESULTS: Forty-three percent of the patients had early-stage disease (stage I or II). Five-year survival for stages I through IV was 95%, 86%, 82%, and 52%, respectively. The incidence of occult cervical metastases for clinical stage I patients was 21%. For clinical stage II patients, the incidence was 62%. Local control of patients treated with surgery alone was 81%. The regional control rate for these patients was 71%. In patients where negative margins were achieved (> or = 5 mm), the local recurrence rate was 13%, regardless of T stage. Eleven percent of the patients underwent a course of postoperative radiotherapy; all had stage IV disease. When compared with advanced-stage patients undergoing surgery alone, there was a significantly improved regional control rate and a trend toward enhanced survival in the patients receiving adjuvant radiotherapy. CONCLUSIONS: There is a significantly high incidence of occult metastatic disease (21%) for T1 lesions or greater in floor of mouth cancer to warrant elective treatment of regional lymphatics. In patients treated with surgery alone with negative margins, the local control rate was 90% versus 62% when the margins were close or positive. Adjunctive radiotherapy showed a statistically significant (p = .005) increased regional control in patients with stage IV disease. Adjunctive radiotherapy is warranted for increased regional control of disease; good local control can be achieved in floor of mouth cancer with surgery alone when negative margins are obtained.     

Thymoma: prognostic factors and treatment outcomes

BACKGROUND: The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy. METHODS: Seventy patients treated at the University Hospital Düsseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test. RESULTS: In univariate analysis, KPS (P < 0.001), histologic type (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy. CONCLUSIONS: Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.     

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity

Over a 14-year period, from 1971 to 1985, there were 15 patients referred to the Princess Margaret Hospital in Toronto for postoperative radiotherapy to the cervical lymph nodes following radical neck surgery for metastatic cancer. An intensive investigation failed to yield a primary site in any patient. All of the patients had extensive neck disease with significant indications for postoperative radiotherapy (massive neck nodes, invasion of extra nodal structures or fixation to unresectable adjacent structures). Of this highly selected group of patients with advanced neck disease: 4/15 (27%) died within one year of uncontrolled local disease, a further 2/15 (13%) died within four years of metastatic/recurrent disease, 6/15 (33%) died of intercurrent disease and 3/15 (20%) were alive with at least four years follow-up. Although all patients presented with advanced disease, survival and significant palliation was possible in this select group of patients.     

Function-sparing surgery for desmoid tumors and other low-grade fibrosarcomas involving the brachial plexus

OBJECTIVE: Low-grade fibrosarcomas and desmoid tumors present a surgical challenge in that they have a strong tendency for local invasion, surgical margins are poorly delineated, and complete resections are difficult. Nowhere is this more evident than in those lesions involving the brachial plexus. We review our experience with these difficult lesions. METHODS: From a prospective database of 2900 patients admitted for treatment of sarcoma between 1982 and 1996, we identified 15 patients with involvement of the brachial plexus by a low-grade fibrosarcoma or desmoid tumor. All patients underwent resection, with 13 of 15 receiving adjuvant radiotherapy. The 15 patients had a mean age at initial operation of 47 years. The male-to-female ratio was 8:7. The mean follow-up period was 65 months (median, 53 mo). RESULTS: Gross total resection was achieved in 12 patients (80%), although 11 of these patients had positive surgical margins. Overall, 64% of the tumors have recurred locally. There were no distant metastases, and no patients died as a result of their disease. One patient died as a result of unrelated cancer. An assessment of the functional outcomes revealed seven patients with normal function or mild neurological deficits and eight who were suffering from significant weakness, debilitation, or chronic pain. One patient required forequarter amputation. CONCLUSION: Surgical resection plus postoperative radiotherapy is the treatment of choice for low-grade fibrosarcomas and desmoid tumors involving the brachial plexus. However, aggressive surgical management with the goal of achieving a gross total resection with negative histological margins can produce unnecessary morbidity. Preserving function should be a primary goal of the operations, although this will be associated with residual disease and will risk local recurrence but rarely death resulting from the disease.     

Limb salvage and outcome of osteosarcoma. The University of Muenster experience

One hundred thirty-six patients with non-metastatic high grade osteosarcoma treated from 1978 to 1994 in one institution with a multidisciplinary approach that included intravenous neoadjuvant chemotherapy were studied to evaluate which factors influence the outcome of modern orthopaedic therapy. Anatomic location, tumor volume, surgical margins, complications, and functional outcome were analyzed. Seventy-nine patients had a limb salvage procedure, 21 had a rotationplasty, and 33 had an amputation. Limb salvage consisted of 32 endoprostheses, 39 allograft replacements, six autograft replacements, and two shortening procedures. Three patients died during preoperative chemotherapy treatment. At a mean followup of 43 months, 81 patients continue to be disease free, three are alive after local recurrence, 17 are alive after having metastatic lesions, five are alive with metastatic lesions present, and 30 patients died of their disease. Forty-seven patients had pulmonary metastatic lesions, 14 had osseous metastatic lesions, three had abdominal metastatic lesions, two had lymphatic metastatic lesions, and eight patients had skip metastatic lesions. Prognosis correlated with chemotherapy response, surgical margins, and tumor volume. The minor complication rate for limb salvage was 4% and the major complication rate was 52%. Amputations had a 6% minor complication rate and 34% major complication rate. Rotationplasties had 10% minor and 48% major complication rates. The Musculoskeletal Tumor Society functional evaluation after limb salvage showed that 23 (38%) patients had more than 75% of the maximum functional score, 34 (56%) were from 50% to 75%, and three (5%) less than 50%. Of the rotationplasties, six (67%) were functionally better than 75% and three (33%) were functionally better than from 50% to 75%. In the group of amputations, 13 (56%) were from 50% to 75%, and 10 (44%) less than 50%. The extent of preoperative necrosis, surgical margins, and tumor volume are the most important prognostic factors. The increase in limb salvage procedures and the better long term survival of patients results in a higher rate of immediate and delayed complications. Functional outcome after rotationplasty is superior to limb salvage reconstruction and amputation.     

Results of postoperative radiotherapy in the treatment of sarcoma of the corpus uteri

BACKGROUND: The role of radiotherapy in the treatment of uterine sarcoma still is not clear. Data from the literature advocating adjuvant radiotherapy most often are based on very small patient groups, whereas larger epidemiologic studies, which appear to show no benefit for the additional radiotherapy, lack information regarding clinical data influencing the choice for adjuvant irradiation. METHODS: During 1981-1992, 72 patients were referred for postoperative radiotherapy. Histologic diagnoses were leiomyosarcoma (LMS) in 30 patients, endometrial stromal sarcoma (ESS) in 11 patients, mixed müllerian tumors (MMT) in 28 patients, and other sarcoma types in 3 patients. The 1988 International Federation of Gynecology and Obstetrics classification for endometrial carcinoma was applied retrospectively. Forty patients presented with Stage I disease, 9 with Stage II, 17 with Stage III, and 6 with Stage IV. External beam therapy was given with a cobalt-60 unit using a rotation technique with 2 separate arcs in daily fractions of 2 gray (Gy), up to a total dose of 56 Gy to the pelvis. Brachytherapy was given to the vaginal vault either with 2 radium applications (median: 1600 milligram-hours to the applicator surface) or, in the majority of cases, with 3 fractions of high dose rate afterloading applications (iridium-192, 10-Curie source) with 7 Gy each to an isodose 7.5 mm from the applicator surface. RESULTS: The 5-year actuarial overall survival, disease specific survival, and local control rates for 72 patients were 52.3%, 58.5%, and 77.9%, respectively; in Stage I patients they were 74.8%, 84.6%, and 94.4%, respectively; in Stage II patients they were 53.3%, 53.3%, and 88.9%, respectively; in Stage III patients they were 15.7%, 17.9%, and 55.5%, respectively; and in Stage IV patients they were 0%, 0%, and 0%, respectively. For LMS, the 5-year actuarial overall survival, disease specific survival, and local control rates were 49.4%, 52.0%, and 76.0%, respectively; for ESS they were 81.8%, 81.8%, and 90.9%, respectively; and for MMT they were 42.3%, 54.9%, and 72.4%, respectively. CONCLUSIONS: These data suggest that adjuvant radiotherapy is an effective treatment for uterine sarcoma with regard to disease specific survival in patients with early stage disease and increases local control, even in patients with advanced stage disease.     

Modified type IV-V radical hysterectomy with systematic pelvic and aortic lymphadenectomy in the treatment of patients with stage III cervical carcinoma. Feasibility, technique, and clinical results

BACKGROUND: Due to the high prevalence of perioperative major morbidity and the difficulties in achieving surgical disease free margins, surgery has had no role in the treatment of patients with Stage III cervical carcinoma. METHODS: Forty-two women with International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical carcinoma responding to platinum-based neoadjuvant chemotherapy underwent the maximum surgical effort, comprised of a modified type IV-V radical hysterectomy (37 patients) or anterior pelvectomy (5 patients) with systematic pelvic and aortic lymphadenectomy. Feasibility, modifications of surgical technique, and pathologic and clinical data were analyzed. RESULTS: Surgery was feasible in all 42 patients intraoperatively selected. Disease free margins were achieved in all but one patient. The median operating time was 390 minutes, and the median estimated blood loss was 800 mL. In the last series of patients, these figures declined to 320 minutes and 600 mL, respectively. Major morbidity consisted of severe intraoperative hemorrhage in two patients, pulmonary embolism in four, ureteral fistula in three, and laparocele in three. The number of lymph nodes removed ranged from 30 to 117 with a median of 56. The mean lengths of vagina and lateral parametrium resected were 55 and 48 mm, respectively. Despite perioperative chemotherapy, lymph node metastasis was present in 36% of patients, parametrial disease in 38%, and vaginal disease in 45%. After a median follow-up of 53 months, the 5-year overall and disease-free survival rates of radically operated patients were 70% and 58%, respectively. CONCLUSIONS: Thanks to improved surgical technique and perioperative care, extended radical surgery appears to be feasible with acceptable morbidity in chemosensitive women with Stage III cervical carcinoma and may constitute a valid alternative to radiotherapy in these patients.     

Phase I/II study of the CAPABLE regimen for patients with poorly differentiated carcinoma of the nasopharynx

PURPOSE: To evaluate the role of aggressive combination chemotherapy in patients with poorly differentiated carcinoma of the nasopharynx (NPC). PATIENTS AND METHODS: In a prospective phase I/II study, 90 chemotherapy-naive patients with NPC (21 with very advanced locoregional disease, 18 with locoregional persistent and/or recurrent disease postradiotherapy, and 51 with metastatic disease) were treated with cyclophosphamide, doxorubicin, cisplatin, methotrexate, and bleomycin (CAPABLE). Two schedules of this regimen were used over a 9-year period, with the second schedule being a modification of the first in an attempt to minimize treatment-related toxicity. RESULTS: Of 21 patients with very advanced local disease, one had a complete response (CR) and 17 had partial responses (PRs) (response rate, 86%). Seventeen of these 21 patients had subsequent radiotherapy. Of 17 patients with measurable locoregional disease either persistent and/or recurrent postradiotherapy, there were four CRs and three PRs (response rate, 41%). Of 44 patients with measurable metastatic disease, there were three CRs and 32 PRs (response rate, 80%). The median survival durations for these three groups of patients were 47, 16, and 14 months, respectively. The two chemotherapy schedules had similar received dose-intensities (RDIs) and produced similar response rates and survival. Toxicity was severe with frequent mucositis and myelosuppression. Overall, 37 patients required at least one hospital admission for management of toxic side effects and there were seven drug-related deaths. Three of the deaths were due to fulminant hepatitis, likely from reactivation of hepatitis B. CONCLUSION: This aggressive regimen provides a high rate of tumor response, but limited palliation for most patients with recurrent or metastatic NPC. The results with chemotherapy followed by radiotherapy for patients with very advanced local disease are encouraging, but proof of benefit would require evaluation in a randomized trial.     

The calretinin-containing mossy cells survive excitotoxic insult in the gerbil dentate gyrus. Comparison of excitotoxicity-induced neuropathological changes in the gerbil and rat

BACKGROUND: The locoregional failure rate remains high in advanced cervical carcinoma. Chemotherapy (CT) was added to radiotherapy (RT) in order to increase disease control and to improve 5-year survival. METHODS: CT + RT included cisplatin administered 100mg/m2, d.1 plus 5-fluorouracil 1000 mg/m2 D.1 to 5, ci (120 hrs), q every 3rd week for 3 cycles, followed by RT. RT included external beam irradiation 64.8 Gy in 1.8 Gy fractions, five days a week, by 4-field box technique. The median follow-up was 46 months. Ninety-four patients were evaluable for survival, 47 in the CT + RT group and 47 in the RT group. Ninety-two patients were evaluable for response. Known prognostic factors were equally distributed between the two groups. RESULTS: Of the 43 patients evaluable before RT, 31 (72%) achieved a partial or complete response after CT alone. After RT, 52 patients attained a complete response, 25 in the CT + RT group and 27 in the RT-group. Sixty-three patients developed distant metastases or local relapse, 30 in the CT + RT group and 33 in the RT group. In the CT + RT group 6 of the 9 patients with metastases also had local progression at relapse, in the RT group, 7 of 17 patients. The survival rates for the two groups are not statistically different. Thirty-seven patients are alive, 29 have no evidence of disease. Fifty-seven have died, 29 in the CT + RT group and 28 in the RT group. Fifty-four deaths were related to cancer, and 3 to therapy. CONCLUSIONS: Sequential CT and RT did not improve the survival, local control, or metastasis rate compared with RT alone.     

Serum creatine kinase in fasciocutaneous and musculocutaneous flap surgery

BACKGROUND: Stage III and IV squamous cell cancers of the head and neck are often unresectable at presentation and are associated with poor disease-free and overall survival rates. A phase II study using concurrent cisplatin and radiotherapy in advanced head and neck cancer indicated impressive local-regional control and survival with organ preservation. METHODS: A multicentered phase II study was undertaken consisting of 1.8 Gy fraction radiotherapy for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.8 Gy. Continuous infusion cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Biopsy of the primary tumor was done at this point, and patients with clinical and pathologic complete response continued with hyperfractionated radiotherapy to 75.6 Gy plus simultaneous carboplatin 25 mg/m2 BID for 12 consecutive days. Residual disease at 46.8 Gy required curative surgery. RESULTS: Seventy-four patients entered the study, and 73 completed their treatment. Twenty were stage III and 54 were stage IV. Fifty patients had involved regional lymph nodes. Treatment was well tolerated with only one grade IV hematologic toxicity. At 46.8 Gy, biopsy revealed a complete response in 75% of the primary sites and 47% of the nodes. Only 12 patients required resection of the primary lesion. At 4 years (median follow-up is 26 months), 29 patients have recurred. CONCLUSIONS: Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in stage III and IV head and neck cancer yields excellent local-regional control with organ preservation. This protocol is intensive, and some patients have distant failures.     

Childhood soft tissue sarcoma: a 20-year experience

PURPOSE: To evaluate the disease-free and overall survival of pediatric patients with nonrhabdomyosarcoma soft-tissue sarcomas. METHODS: We retrospectively analyzed the records of 67 pediatric patients with a diagnosis of nonrhabdomyosarcoma soft tissue sarcoma treated with curative intent between 1970 and 1992. Median follow-up time for the 52 survivors was 120 months (range, 7 to 277 months). Fifty-nine patients received external beam radiotherapy, in a median dose of 5400 cGy (range, 1800 to 6660 cGy.) All patients underwent an initial surgical procedure. Eighteen patients had gross residual disease, and 15 had gross total excision with microscopic residual disease or positive margins. Adjuvant chemotherapy was administered to 44 patients (65%). RESULTS: The actuarial 10-year freedom from progression or recurrence and overall survival rates were 76% and 75%, and the 20-year rates were the same. Of 18 patients with gross residual disease, 9 (50%) had local progression and 6 died of local-only disease. By contrast, only one patient with microscopic residual disease who received postoperative radiotherapy had a local recurrence. The disease-free survival rate also correlated with histologic grade. CONCLUSIONS: As with adult soft tissue sarcomas, gross residual disease predicts local failure. Our results suggest that pediatric patients with soft tissue sarcomas treated with surgery and postoperative radiotherapy generally have a favorable overall survival rate.     

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial

CONTEXT: For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone. However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established. OBJECTIVE: To determine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival. DESIGN: Multicenter, randomized, parallel group trial. SETTING: University-affiliated cancer treatment facilities. PATIENTS: Ninety-five patients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study. INTERVENTIONS: Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median follow-up of 48 weeks and 43 weeks, respectively. MAIN OUTCOME MEASURES: The primary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently. RESULTS: Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; P<.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; P<.01). Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P=.003). There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent. CONCLUSIONS: Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.     

Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study

PURPOSE: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma. METHODS AND MATERIALS: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I--14, Stage II--40, Stage III--27, Stage IVA--5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m2/day for 96 hours and cisplatin 50 mg/m2 in weeks 1 and 5. RESULTS: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3-4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I--50%, Stage II--39%, and Stage III/IVA--38%. CONCLUSIONS: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.     

Vitamin D3, lactose, and xylitol stimulate chromaffin cell proliferation in the rat adrenal medulla

We tested paclitaxel (Taxol) and low dose hydroxyurea as second line therapy in 30 patients with non-small cell lung cancer since both drugs are active against non-small cell lung cancer in other settings, and since hydroxyurea may reverse chemotherapy resistance by disrupting double minute chromosomes. Hydroxyurea 500 mg was given orally each Monday, Wednesday, Friday starting 1 week before paclitaxel, and continuing until removal from study. Paclitaxel 135 mg/m2 was given i.v. over > or = 1 h every 3 weeks with dexamethasone, diphenhydramine, and ranitidine. Patients could have paclitaxel doses escalated to 175 mg/m2 in course 2 and to 200 mg/m2 in course 3, where tolerated. Sixteen males and 14 females were treated. All patients had previously received a single cisplatin-based chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients had adenocarcinomas, six had squamous cell carcinomas, and 12 had large cell carcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. Paclitaxel doses were 135 mg/m2 in 56 courses, 175 mg/m2 in 24, and 200 mg/m2 in 15. Treatment was well tolerated. Median granulocyte nadirs were 2.5 (x 10(9)/l) for paclitaxel 135 mg/m2, 1.8 for 175 mg/m2, and 1.3 for 200 mg/m2. No patient developed febrile neutropenia, and none required a dose reduction. Two patients had reversible anaphylaxis. Other toxicities were quite tolerable. They included fatigue, myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis, flushing, headache, swollen red hands, and anxiety. One patient had a partial remission and 15 had stable disease (including six with minor responses). Median survival was 20 (95% CI, 12-34) weeks, with 19% of patients remaining alive at 1 year from initiation of treatment. This is a well-tolerated regimen with modest activity as second line chemotherapy for patients with non-small cell lung cancer previously treated with cisplatin regimens. Higher doses would be feasible and other strategies are now being explored.