Twelve-year follow-up of trimodality therapy for stage IIIA non-small cell lung cancer.

Non-small cell carcinoma of the lung (NSCLC) remains a formidable problem with a poor 5 year survival for stage III patients. Between 1985-1991, 53 patients with biopsy proven Stage IIIA NSCLC were treated with a trimodality treatment program. Chemotherapy, consisting of two cycles of continuous infusion cisplatinum and bolus etoposide, was started on days 1 and 28 of radiation therapy (54 Gy + 5.4 Gy boost in 6 1/2 weeks) directed to the lung primary and mediastinum. Four to six weeks after radiation therapy, patients underwent thoracotomy for radical pulmonary resection. Three weeks post surgery, the same chemotherapy was repeated for two cycles every 28 days. Forty-seven out of 53 patients (89%) achieved a clinical response after induction chemoradiation. Of these 47 patients, 33 underwent thoracotomy and 27 of them completed surgical resection. Treatment was well-tolerated. All surviving patients have no or minimal respiratory toxicities. With a median follow up of 9 1/2 years, surgically treated patients have a disease specific survival of 42% at 12 years. One patient survived beyond 9 years without surgery. Concurrent chemoradiation plus surgery is well tolerated and offers patients with Stage IIIA NSCLC significant long term survival benefit and warrants further assessment in a randomized trial.

Breast augmentation with fresh-frozen homologous fat grafts.

The purpose of this report is to present a patient who underwent breast augmentation with fresh-frozen fat homografts in Russia 10 years ago, despite the publication of major complications following this procedure.

Caregiver and elder experiences of Cambodian, Vietnamese, Soviet Jewish, and Ukrainian refugees.

Our purpose was to describe and compare Cambodian, Vietnamese, Soviet Jewish, and Ukrainian refugee caregivers and elders on life experiences, health status, and knowledge of available services. Detailed interviews were conducted with 105 female caregivers and 52 elders. Similar patterns emerged across all groups with regard to filial obligation, minimal knowledge of services, impact of immigration, and retention of cultural ties. Findings confirmed the special health and social service needs of refugee families in transition.

Late effects of therapy in 94 patients with localized rhabdomyosarcoma of the orbit: Report from the Intergroup Rhabdomyosarcoma Study (IRS)-III, 1984-1991.

BACKGROUND: We reviewed the late complications of therapy in 94 patients with localized, primary rhabdomyosarcoma of the orbit treated on the Intergroup Rhabdomyosarcoma Study (IRS)-III protocol (1984-1991). PROCEDURE: A questionnaire was sent to the institutions that had registered 106 patients with orbital RMS on the IRS-III protocol, seeking information about vision, periocular structures, and growth and development of the 102 survivors. RESULTS: Ninety-four questionnaires were returned. The median follow-up interval was 7.6 years. The affected eye was removed from 13 patients because of local recurrence (N = 10) or other causes (N = 3). Seventy-nine of the eighty-one remaining patients had received radiation therapy. Sixty-five of these seventy-nine patients (82%) developed a cataract, and 43 of them (66%) underwent cataract surgery. Fifty-five patients (70%) had decreased visual acuity. Twenty-four patients had a dry eye, and 22 had chronic keratitis, conjunctivitis, or corneal changes. Strabismus, diplopia, retinopathy, and uveitis were uncommon. The orbit was hypoplastic in 48 of 82 patients assessed (59%). Ptosis and enophthalmos were reported in 22 patients. Decreased statural growth was noted in 13 of the 53 irradiated patients aged 3-14 years at diagnosis with sufficient data (24%). CONCLUSIONS: The overall survival rate was 96% (102/106). The eye was preserved in 86% of the patients, but vision was impaired in 70% of them. Other frequent complications were cataract, orbital hypoplasia, keratoconjunctivitis, and ptosis/enophthalmos. The current IRS-V study recommends decreasing the dose of irradiation and using conformal techniques in an attempt to minimize these complications.

Preoperative chemotherapy-sensitized radiation therapy for cervical metastases in head and neck cancer.

OBJECTIVE: To determine the efficacy of concurrent preoperative cisplatin chemotherapy and radiotherapy (CT/RT) for patients with advanced head and neck cancer and cervical metastatic disease. DESIGN: Retrospective analysis. SETTING: University hospitals. PATIENTS: Eighty-eight patients with operable stage III and IV squamous cell carcinoma of the head and neck and palpable cervical lymphogenous metastases received preoperative concurrent CT/RT followed by planned neck dissection. INTERVENTIONS: All patients undergoing CT/RT received concomitant continuous infusions of cisplatin (20 mg/m2) on days 1 to 4 and 22 to 25 of CT/RT. Thirty-nine patients underwent single-fraction (1.8-Gy) radiotherapy to 45.0 Gy, and 49 patients received 10 single-fraction (1.8-Gy) treatments, which were hyperfractionated (1.2-Gy twice a day) to 46.8 Gy. MAIN OUTCOME MEASURES: The 71 patients for whom complete post-CT/RT data were available were evaluated for clinical response in addition to survival. Histologic complete response (HCR) was confirmed from planned neck dissection specimens (n = 48) after clinical complete response (CCR) from initial CT/RT. Kaplan-Meier statistical analysis for disease-specific survival and overall survival was performed on all 88 patients who received CT/RT. RESULTS: A CCR and an HCR were noted in 78% (18/23) and 59% (10/17) of patients with N1 lesions, respectively, and in 60% (29/48) and 45% (14/31) of patients with N2-3 lesions, respectively. The percentage of patients with CCR who also had HCR was 67% (10/15) for patients with N1 lesions and 54% (14/26) for patients with N2-3 lesions. With a median follow-up of 18.5 months, the Kaplan-Meier disease-specific survival rate at 54 months (n = 88) was 70% (21/30) for patients with N1 lesions, 60% (24/40) for patients with N2 lesions, and 39% (7/18) for patients with N3 lesions. The overall survival and disease-specific survival rates at 5 years for all nodal groups combined were 36% (32/88) and 59% (52/88), respectively. CONCLUSIONS: A CCR to CT/RT was achieved in nearly two thirds of patients with head and neck cervical lymphogenous metastases, independent of nodal tumor load. Most patients (59% [24/41]) with CCR were pathologically tumor free before neck dissection.

Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer.

HYPOTHESIS: Neoadjuvant therapy has the potential to induce regression of high-risk, locally advanced cancers and render them resectable. Preoperative chemoradiotherapy is proposed as a testable treatment concept for locally advanced pancreatic cancer. DESIGN: Fourteen patients (8 men, 6 women) with locally advanced pancreatic cancer were surgically explored to exclude distant spread of disease, to perform bypass of biliary and/or gastric obstruction, and to provide a jejunostomy feeding tube for long-term nutritional support. A course of chemotherapy with fluorouracil and cisplatin plus radiotherapy was then initiated. Reexploration and resection were planned subsequent to neoadjuvant therapy. MAIN OUTCOME MEASURES: Tumor regression and survival. INTERVENTIONS: Surgically staged patients with locally advanced pancreatic cancer were treated by preoperative chemotherapy with bolus fluorouracil, 400 mg/m2, on days 1 through 3 and 28 through 30 accompanied by a 3-day infusion of cisplatin, 25 mg m2, on days 1 through 3 and 28 through 30 and concurrent radiotherapy, 45 Gy. Enteral nutritional support was maintained via jejunostomy tube. RESULTS: Of 14 patients who enrolled in the protocol and were initially surgically explored, 3 refused the second operation and 11 were reexplored; 2 showed progressive disease and were unresectable and 9 (81%) had definitive resection. Surgical pathologic stages of the resected patients were: Ib (2 patients), II (2 patients), and III (5 patients). Pancreatic resection included standard Whipple resection in 1 patient, resection of body and neck in 1 patient, and extended resection in 6 patients (portal vein resection in 6, arterial resection in 4). One patient who was considered too frail for resection had core biopsies of the pancreatic head, node dissection, and an interstitial implant of the tumorous head. Pathologic response: 2 patients had apparent complete pathologic response; 1 patient had no residual cancer in the pancreatectomy specimen, the other patient who had an iridium 192 interstitial implant had normal core biopsies of the pancreatic head. Five patients had minimal residual cancer in the resected pancreas or microscopic foci only with extensive fibrosis, and 2 patients had fully viable residual cancer. Lymph node downstaging occurred in 2 of 4 patients who had positive peripancreatic nodes at the initial surgical staging. There was 1 postoperative death at 10 days. Sepsis, prolonged ileus, and failure to thrive were major complications. In the definitive surgery group the median survival was 19 months after beginning chemoradiotherapy and 16 months after definitive surgery. The absolute 5-year survival was 11% of 9 patients, 1 is surviving 96 months (with no evidence of disease) after chemoradiotherapy and extended pancreatic resection including resection of the superior mesenteric artery and the portal vein for stage III cancer. In the nonresected group the mean survival was 9 months (survival range, 7-12 months) after initiation of chemoradiotherapy. CONCLUSION: A pilot study of preoperative chemoradiotherapy with infusional cisplatin and radiation induced a high rate of clinical pathologic response in patients with locally advanced pancreatic cancer and merits further study in these high-risk patients.

Interobserver variability in the detection of cervical-thoracic Hodgkin's disease by computed tomography.

PURPOSE: Computed tomography (CT) scans of the neck and chest are obtained at diagnosis of Hodgkin's disease to establish disease extent, plan radiotherapy, and serve as baseline studies for subsequent evaluation of response to therapy. However, differences in interpretation may occur even among experienced radiologists. This study was designed to test the extent of variation among expert radiologists' interpretations and to assess how their interpretations differed from that of the primary (institutional) radiologists. MATERIALS AND METHODS: Five radiologists independently reviewed randomly selected CT scans of 59 patients enrolled onto two Pediatric Oncology Group Hodgkin's disease treatment protocols. For each patient, 31 potential disease sites were scored as positive, negative, uncertain, or unassessable. Agreement among the reviewers and between the reviewers and the primary readers was analyzed. RESULTS: For 58% of the sites, at least four of the five reviewers agreed in >/= 80% of the cases. Kappa analysis showed moderate agreement in approximately two thirds of the sites and poor agreement in the remainder. There was moderate agreement between a majority of the expert readers and the primary radiologist reports for approximately one third of the sites, and agreement was poor in two thirds. CONCLUSION: There are disparities among radiologists' interpretations of cervical-thoracic CT imaging of patients with Hodgkin's disease. This variability may affect patient care and the performance and results of multi-institutional clinical trials. We propose that a standardized method of reporting might improve the consistency of interpretation of CT scans in these patients.

Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the Intergroup Rhabdomyosarcoma Studies (IRS)-II and - III. IRS Group of the Children's Cancer Group and the Pediatric Oncology Group.

BACKGROUND: This review of children and adolescents with nonorbital soft-tissue sarcoma of the head and neck was undertaken to describe late sequelae of treatment, as manifested primarily by problems with statural growth, facial and nuchal symmetry, dentition, vision and hearing, and school performance. PROCEDURE: Four hundred sixty-nine patients entered the IRS-II and -III protocols with localized, nonorbital soft-tissue sarcomas of the head and neck from 1978 through 1987. Their overall survival rate was 53% (250/469) at 5 years. Two hundred thirteen patients were surviving relapse-free 5 or more years after diagnosis, for whom there were serial height measurements at 2 or more years after initiation of therapy. Their median age at diagnosis was 5 years; the median length of follow-up was 7 years. All received multiple-agent chemotherapy, and all but 3 received irradiation to the primary tumor volume. Sixty-eight percent of the tumors arose in cranial parameningeal sites, 22% in nonparameningeal sites, and 10% in the neck. We reviewed flow sheets submitted to the IRS Group Statistical Office to ascertain which late sequelae were recorded. RESULTS: One hundred sixty-four patients (77%) had one or more problems recorded. One hundred ninety of the two hundred thirteen patients (89%) were under 15 years of age at study entry, and at follow-up 92 (48%) had failed to maintain their initial height velocity, which had decreased by more than 25 percentile points from the original value. Thirty-six of the one hundred ninety patients (19%) were receiving growth hormone injections. Hypoplasia or asymmetry of tissues in the primary tumor site was reported in 74 patients, and 13 underwent reconstructive surgery. Poor dentition or malformed teeth were noted in 61 patients. Impaired vision developed in 37 patients, owing primarily to cataracts, corneal changes, and optic atrophy. Thirty-six patients had decreased hearing acuity, and 9 were fitted with hearing aids; 5 of these 9 had received cisplatin. Thirty-five patients were noted to have problems learning in school. Four patients developed a second malignancy (two sarcomas, one carcinoma, one leukemia). CONCLUSIONS: Late sequelae affected the majority of these patients treated for soft-tissue sarcoma of the head and neck on IRS-II and -III. The potential impact of certain sequelae could be reduced by specific measures, such as surgical reconstruction and hormonal therapy. Late sequelae must be taken into account in designing future curative treatments.

Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data.

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.

Accelerated prenatal diagnosis of fragile X syndrome by polymerase chain reaction restriction fragment detection.

Prenatal diagnosis of fragile X syndrome requires detection of the full FMR1 mutation in chorionic villus or amniotic fluid cell samples. Although analysis of genomic DNA restriction fragment pattern is a highly reliable technique for identification of the full FMR1 mutation, standard Southern blot determination of this pattern requires significantly more genomic DNA than is initially available from a prenatal sample. To overcome this limitation we developed a method that determines the diagnostic pattern of genomic restriction fragments from a fraction of a prenatal specimen. The prenatal DNA sample is first digested with EcoRI and EagI, and after agarose gel electrophoresis, the 2- to 10-kb region of the gel is serially sectioned and amplified by polymerase chain reaction. Analysis of prenatal samples from an unaffected male and from a full mutation male showed that this approach generated a diagnostic pattern comparable with a Southern blot of 100-fold more material. This innovation enables laboratories to prenatally diagnose the full FMR1 mutation sooner than standard techniques.

The impact of radiation therapy on quality of life in patients with cancer.

PURPOSE: This study was conducted to evaluate the physical and mental status change during and after a course of radiation treatment in patients with cancer. DESCRIPTION OF STUDY: Twenty-four patients with various malignant diseases were enrolled, including 9 men and 15 women, whose median age was 64.5, to receive radiation therapy. All patients also received psychosocial support from nurses, social workers, and/or organized support groups. The Rand 36-item survey 1.0 (SF-36) was completed at the beginning, the second week, the completion of treatment, and 1 and 3 months after treatment for the evaluation of physical component scores and mental component scores. Karnofsky performance scale and toxicity scores were determined by the treating nurses and physicians. RESULTS: The physical component scores of evaluated patients before treatment were approximately 20% lower than those of the general U.S. population, whereas mental component scores were similar to those of the general U.S. population. After treatment started, Karnofsky performance scale decreased concurrently with an increased rate of toxicity. Both physical and mental component scores were relatively stable throughout the course of evaluation. Mental component scores were the only predictor of toxicity during the treatment. Karnofsky performance scale dropped to their lowest point at the completion of treatment and then improved at 1-month follow-up. CLINICAL IMPLICATIONS: The patients who had higher mental component scores before treatment appeared to have higher, and improving, physical component scores throughout the course of evaluation. Along with complementary social support, the implementation of psychosocial support early and throughout the course of treatment may result in physical benefits and improving overall quality of life. Care should also be taken to make psychosocial support available to patients after the completion of treatment.

A multidisciplinary study investigating radiotherapy in Ewing's sarcoma: end results of POG #8346. Pediatric Oncology Group.

PURPOSE: To determine if involved field radiation (IF) is equivalent to standard whole bone radiation (SF) in local tumor control; to establish patterns of failure following treatment; and to determine response, event-free survival (EFS), and overall survival rates from multidisciplinary therapy in Ewing's sarcoma. METHODS AND MATERIALS: Between 1983 and 1988, 184 children with Ewing's sarcoma were enrolled onto Pediatric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibility criteria; 6 had pathology other than Ewing's sarcoma. Induction chemotherapy of cyclophosphamide/doxorubicin (adriamycin )(C/A) x 12 weeks was followed by local treatment either surgery or radiation therapy and C/A, dactinomycin, and vincristine for 50 weeks. Resection was advised for patients with small primary tumors if accomplished without functional loss. Forty patients were randomized to receive SF, whole bone radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or IF to 55.8 Gy, and the remainder were assigned to IF radiation. RESULTS: Of 178 eligible patients, 141 (79%) had localized disease and 37 (21%) had metastases at presentation. Their 5-year EFS was 51% (SE 5%) and 23% (SE 7%) respectively. The response rate to induction chemotherapy was 88% (28% complete, 60% partial), but after radiotherapy the response rate increased to 98%. Thirty-seven of the localized patients underwent resection, of whom 16 (43%) required postoperative radiotherapy; the 5-year EFS of these surgical patients was 80% (SE 7%). The remaining 104 localized patients were eligible for randomization or assignment to receive radiotherapy; the 5-year EFS of these patients was 41% (SE 5%), with no significant difference in EFS between those randomized to SF vs. IF. Site of primary tumor correlated with 5-year EFS: distal extremity 65% (SE 8%), central 63% (SE 10%), proximal extremity 46% (SE 8%), and pelvic-sacral 24% (SE 10%) (p=0.004). Initial tumor size did not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local failure, while 40% had a systemic failure. The 5-year local control rate for the surgical patients +/- postoperative radiotherapy was 88% (SE 6%), while for the patients undergoing radiotherapy alone it was 65% (SE 7%). There was no difference in local control between those randomized to SF vs. IF. The 5-year local control rate for the patients with pelvic-sacral tumors was 44% (SE 15%), significantly worse than the local control rates for those with central tumors 82% (SE 8%), distal extremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p=0.023). However, quality of radiotherapy correlated with outcome. Patients who had appropriate radiotherapy had a 5-year local control of 80% (SE 7%), while those with minor deviations had 5-year local control of 48% (SE 14%), and those with major deviations had a local control of only 16% (SE 15%) (p=0.005). The local failure was within an irradiated volume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 14%. CONCLUSIONS: As most failures in Ewing's sarcoma are systemic, improved EFS requires more effective systemic chemotherapy. Adequate IF radiotherapy requires treatment to appropriate volumes as defined by MRI imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate tumor volumes, as well as use of conformal radiotherapy techniques are important for improved outcome.

Examination of factors associated with instability of the FMR1 CGG repeat.

We examined premutation-female transmissions and premutation-male transmissions of the FMR1 CGG repeat to carrier offspring, to identify factors associated with instability of the repeat. First we investigated associations between parental and offspring repeat size. Premutation-female repeat size was positively correlated with the risk of having full-mutation offspring, confirming previous reports. Similarly, premutation-male repeat size was positively correlated with the daughter's repeat size. However, increasing paternal repeat size was associated also with both increased risk of contraction and decreased magnitude of the repeat-size change passed to the daughter. We hypothesized that the difference between the female and male transmissions was due simply to selection against full-mutation sperm. To test this hypothesis, we simulated selection against full-mutation eggs, by only examining premutation-female transmissions to their premutation offspring. Among this subset of premutation-female transmissions, associations between maternal and offspring repeat size were similar to those observed in premutation-male transmissions. This suggests that the difference between female and male transmissions may be due to selection against full-mutation sperm. Increasing maternal age was associated with increasing risk of expansion to the full mutation, possibly because of selection for smaller alleles within the offspring's soma over time; a similar effect of increasing paternal age may be due to the same selection process. Last, we have evidence that the reported association between offspring sex and risk of expansion may be due to ascertainment bias. Thus, female and male offspring are equally likely to inherit the full mutation.

Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a Cancer and Leukemia Group B study.

PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. CONCLUSION: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment.

Sterilizing a clinitron air-fluidized bed with colistine powder.

After cross-patient infection occurred with the Clinitron bed, we looked for a way to deliver an antibiotic agent into the inner environment of the Clinitron bed through the filtering system in a manner that would sterilize the contaminated microspheres. Multiple cultures of the contaminated microspheres from the Clinitron air-fluidized bed were done, and the infecting microorganisms were identified. The appropriate antibiotic powder was delivered through the filter system of the bed, and the microspheres were recultured after treatment. After an antibiotic powder was administered, the microspheres cultured were sterile. We found that the Clinitron bed can be safely, easily, and inexpensively sterilized and reused by the administration of antibiotic agent through the air filter system. Furthermore resistant bacteria can be treated with antibiotic agent sparingly used in a clinical setting because of toxicity.

A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation.

BACKGROUND: Although previous research has delineated medical, cognitive, and neuropsychologic late effects of central nervous system (CNS) prophylaxis for childhood acute lymphoblastic leukemia (ALL), it has been difficult to draw conclusions about the long term psychosocial sequelae of these treatments due to methodologic problems that led to inconclusive results in past studies. In the current study, the authors examined the long term psychosocial functioning of childhood ALL survivors who had been treated on a Phase III clinical protocol (Cancer and Leukemia Group B [CALGB] 7611) between 1976 and 1979, in which they were randomized to receive either 2400 centigray of cranial radiation (CRT) with intrathecal methotrexate (IT-MTX) or intermediate dose systemic methotrexate (IV-MTX) with IT-MTX. METHODS: One hundred ten survivors of childhood ALL (mean age, 20.8 years) treated on CALGB 7611 who were age 14 years or older and disease free for at least 1 year were studied a mean of 14.7 years after their entry on CALGB 7611. In a telephone interview, a psychosocial assessment battery was administered to the patients, consisting of measures that assessed psychologic, sexual, social, and vocational functioning as well as any delayed physical effects. RESULTS: Survivors who had received CRT + IT-MTX had significantly poorer academic achievement (P = 0.0001), poorer self-images with regard to their bodies (P = 0.001), and greater psychologic distress (P = 0.005). CONCLUSIONS: Cranial radiation used to treat children with ALL has significant long term sequelae in terms of poorer academic achievement and psychosocial functioning. These data add weight to the conclusion that CRT prophylaxis should only be used to treat children who are at high risk of CNS relapse.

Recurrence patterns with concurrent platinum-based chemotherapy and accelerated hyperfractionated radiotherapy in stage III and IV head and neck cancer patients.

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.