External irradiation of macroinvasive pituitary adenomas with telecobalt: a retrospective study with long-term follow-up in patients irradiated with doses mostly of between 40-45 Gy

PURPOSE: Published dose recommendations for radiotherapy in patients with pituitary macroadenomas vary. Therefore, we retrospectively analyzed the results in our patients from the treatment period 1973-1992. METHODS AND MATERIALS: From a total of 89 patients with macroinvasive adenomas, 66 received radiation therapy immediately following subtotal surgical removal (combined treatment modality), and 22 were irradiated as primary treatment or after surgical recurrence. Only one patient was reirradiated. The surgical interventions have been performed by the same surgeon. For the majority of patients (79 out of 89) with a mean follow-up of 8.1 years (0.5-19 years) the total tumor dose ranged between 40-45 Gy at a dose per fraction of 1.8-2.25 Gy. All patients had bilateral opposed fields with telecobalt. Eleven patients had an additional arc rotation. RESULTS: The 10-year progression-free survival for all 89 patients independent of treatment modality was 88.1%. The 10-year progression-free survival for patients treated by surgery and adjuvant radiation therapy (40-45 Gy at 1.8-2.25 Gy, 60 out of 79) was 90.3%, and for radiation therapy alone (40-45 Gy at 1.8-2.25 Gy, 19 out of 79), 100% (p = 0.32). The prognostic factors for progression-free survival were the subtype of adenoma, the presence of visual symptoms at the time of diagnosis, the suprasellar extension, and the initial hormone levels. The presence of infiltration of adenoma cells in the basal dura or in the mucosa of the sinus sphenoidalis do not represent prognostic factors showing the special biological behavior of pituitary adenomas. Signs of x-ray-induced cerebral necrosis have not been observed in any patient. Long-term visual complications developed in four patients. This could be due to scar formation in the treated region, which can compress the optic nerve and provoke disturbance similar to an empty-sella syndrome. The latter occurred prevalently years after treatment, even though surgical methods of sellar plugging were used. The incidence of hypopituitarism after combined treatment modality at time of last follow-up (irradiated between 40-45 Gy at 1.8-2.25 Gy) was low (36%, 21 out of 60). CONCLUSION: In patients with pituitary macroadenomas, radiotherapy with a total dose of 40-45 Gy at 1.8-2.25 Gy per fraction resulted in a high local tumor control without serious morbidity.     

Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas

OBJECTIVE: This prospective clinical trial was undertaken to assess the rate of tumor recurrence in patients with endocrine-inactive pituitary macroadenomas who underwent gross total surgical resection of their tumors and did not receive adjuvant radiotherapy. METHODS: Between December 1987 and July 1994, 45 patients with endocrine-inactive pituitary macroadenomas underwent transsphenoidal surgery. In 38 (84%) of these patients, gross total surgical resection was achieved and was confirmed by postoperative magnetic resonance imaging (n = 37) or computed tomography (n = 1). After receiving counseling from the neurosurgeon concerning the risks and benefits of radiation therapy, 32 of the 38 patients elected not to receive adjuvant radiotherapy. Patients were followed through March 1998 with radiographic imaging obtained every 6 months for the first 2 years, annually for postoperative Years 3 and 4, and then every 2 to 3 years thereafter. The study end point was defined as radiographic tumor recurrence or patient death. RESULTS: The mean follow-up duration for the study group was 5.5 years. During that time, 2 of 32 (6%) patients developed recurrence, at 18 and 24 months, respectively, after initial surgery. Both were successfully treated using radiation therapy, with one requiring additional surgery. Three additional patients died as a result of unrelated causes 9, 12, and 49 months, respectively, after initial surgery. Immunocytochemical analysis revealed 66% of the tumors to be weak gonadotroph cell adenomas, 22% to be null cell adenomas, 9% to be silent prolactinomas, and 3% to be silent corticotroph cell adenomas. CONCLUSION: This study demonstrates a 6% 5-year recurrence rate in patients with endocrine-inactive pituitary macroadenomas treated using gross total surgical resection alone. Reserving radiation therapy for the infrequent patient with recurrence and sparing the majority of patients the associated risks inherent in its use seems reasonable.     

Preoperative criteria for identifying eloquent brain. Intracarotid amytal for language and memory testing

Purpose: to analyze the effect of overall treatment time of radiotherapy on survival and local control in locally advanced prostatic cancer in a split-course treatment setting. Methods and Materials: 168 patients with Stage C prostatic cancer treated during 1979-1989 by the split-course method where the overall treatment time is protracted. Treatment consisted of whole pelvis irradiation of 40 Gy in 4 weeks, followed by a planned 3-week interruption and an additional 26 Gy by the reduced field technique to a total dose of 66 Gy in 9 weeks and 30-33 fractions. The overall treatment time varied from 55 to 100 days. Thirty-eight percent (63) of the patients were treated primarily with radiotherapy, while the rest (105) had received androgen ablative therapy during 2 to 4.5 years before radiotherapy. To examine the effect of treatment time on local control, the patients were divided into three groups ( < or = 63 days, 64-70 days, and > 70 days) by treatment time. Results: the 5-year actuarial survival rates, calculated from the date of diagnosis, were 91% for the hormonally manipulated patients and 69% for the patients treated with radiotherapy alone. The 5-year actuarial local control rates, counted from the start of radiotherapy, were 84% for radiotherapy and 80% for the hormonally manipulated group. Overall, no significant effect of treatment time could be seen, either for radiotherapy alone or for the hormonally manipulated group. The results were similar when the material was further divided by T category and histologic grade. Conclusions: no significant effect of overall treatment time (55 to 100 days) on survival or local control was found in either group. The survival time from diagnosis was longer in the hormonally pretreated group. Apparently, with adequate doses ( > or = 65 Gy) the overall treatment time becomes less important for local control of advanced prostatic cancer, even in a split-course treatment setting.     

In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16% and to 24 +/- 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.     

Hepatocellular carcinoma presenting as extrahepatic mass on computed tomography

Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia-modifying agents during radical radiotherapy for bladder cancer using a standard daily 20-fraction schedule. Three groups of patients have received (a) nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in 20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4 weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4 weeks. Ten patients were treated in each group. All patients completed carbogen and radiotherapy as prescribed, but only 45% completed daily nicotinamide over the 4-week treatment period. The end points of this study were acute bowel and bladder morbidity and local control at cystoscopy 6 months after treatment. An expected level of acute bowel and bladder morbidity was seen that reverted to normal in most patients by 12 weeks with no difference between the three treatment groups. Complete response rates at 6 months were seven out of ten (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It is concluded that carbogen and nicotinamide may improve the results of daily fractionated radiotherapy in bladder cancer and that further evaluation is required.     

The type of local treatment conditions the prognosis in patients with nonmetastatic Ewing's sarcoma of the extremities treated with adjuvant chemotherapy

The results obtained in 172 cases of non metastatic Ewing's sarcoma of the extremities are reported. The patients were advised to undergo surgical treatment, followed by radiotherapy (40-45 Gy) in case of inadequate surgical margins. 48 patients who refused surgical treatment, were locally treated with radiotherapy alone (50-65 Gy). With a mean follow-up of 8 years (R. 3-15) 101 patients (58.7%) are free of disease and 68 relapsed with metastases and/or local recurrence. A radio-induced bone sarcoma developed in two patients, one patient died of ADM cardiomyopathy. No differences in terms of risk factors were observed between patients who were or were not treated with surgery. A better DFS was observed in the patients treated with surgery (66.9%) in comparison with those treated with radiotherapy alone. The higher percentage of local recurrences observed in patients treated with radiotherapy alone seems to be responsible for the worse prognosis observed in these patients. The authors' conclusion is that the local control in patients with non metastatic Ewing's sarcoma should always be achieved by means of surgery.     

Concurrent radiotherapy and chemotherapy with protracted continuous infusion of 5-fluorouracil in inoperable esophageal squamous cell carcinoma

PURPOSE: The feasibility of a concurrent chemoradiotherapeutic protocol for patients with inoperable esophageal squamous cell carcinoma was tested. METHODS AND MATERIALS: Concurrent chemoradiotherapy using protracted low-dose continuous infusions of five-fluorouracil (5-FU; 250-300 mg/m2/24 h) and standard external beam irradiation was given to 28 patients with inoperable esophageal squamous cell carcinoma between November 1991 and June 1993. RESULTS: For 25 patients receiving a total dose of > or = 60 Gy and concurrent 5-FU infusion for more than 5 weeks, the complete response rate was 52%. Local progression-free rate in this chemoradiotherapy group was significantly higher than the historical controls treated by radiotherapy alone (p < 0.05). A multivariate analysis revealed the treatment scheme (concomitant chemoradiotherapy vs. radiotherapy alone) to be a significant factor in local control (p < 0.01). Swallowing pain (39%), anorexia (39%), and nausea (32%) were the most frequent early reactions. Serious late radiation complications have not been observed. CONCLUSION: The concurrent chemoradiotherapy using protracted low-dose continuous infusion of 5-FU and standard radiotherapy is an effective and safe method to obtain a local control in inoperable esophageal squamous cell carcinoma.     

Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas

This study reports the outcome of 70 patients who were treated by a consistent treatment plan of surgery and postoperative radiotherapy (RT) for pituitary macroadenomas in the modern era [computed tomographic scan or magnetic resonance imaging (MRI), dopamine agonist therapy (DA) added as indicated, and immunohistochemical staining]. Sixty-two patients underwent transsphenoidal surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions postoperatively (vs. other dose fractionation schemes). Twenty-four patients received DA for prolactin-secreting tumors. With a median follow-up of 8 years (range 2-15), 68 patients have experienced continuous control of their tumors. Most symptoms related to mass effect abated, while physiologic symptoms such as amenorrhea from markedly elevated prolactin levels tended to persist. Treatment-induced hypopituitarism occurred in 42% of the patients at risk. No patients in this series have died as a result of their pituitary tumor. No gross neuropsychologic dysfunction after treatment has been noted. While it is possible at this time with serial MRI to withhold postoperative RT and observe some patients who have had a "gross total" resection of a macroadenoma, the therapeutic ratio for surgery and adjuvant radiotherapy for patients with nonfunctional tumors as well as select patients with secretory macroadenomas is favorable.     

Treatment of pituitary adenoma]

RECOMMENDED TREATMENTS: The different therapeutic strategies proposed for pituitary adenomas are relatively well-known thanks to numerous studies evaluating their effect on outcome. Unfortunately, large comparative clinical trials are difficult to construct due to the small number of cases of this rare condition. Therapeutic recommendations are thus generally based on the opinion of recognized experts. MICROADENOMA: Small (< 10 mm) prolactin-secreting adenomas should be treated surgically, generally by transsphenoidal adenomectomy, or medically by dopaminergic agonists: bromocriptin, quinagolide or cabergolin (the two latter drugs are more effective and better tolerated than their parent compound bromocriptin). MACROADENOMA: The expected success rate for surgical treatment of macroadenomas is low and dopaminergic agonists is generally recommended (including cases with visual impairment since the effect can be very rapid). Prolactin levels can be lowered and tumor volume reduced (in > 70% of cases). ACROMEGALY: Surgery is the firs intention treatment for acromegaly. In case of unsuccessful surgery (the criteria for "cure" are much more strict in 1998 than previously), somatostatin analog and/or hypothalamo-hypophyseal radiotherapy are recommended. Slow release formulations of somatostatin analogs can now be given by monthly (octreotide LP) or biweekly (lanreotide LP) injections. CUSHING'S DISEASE: Cure can be achieved in > 80% of cases with surgery, the first intention treatment of choice. If surgery is unsuccessful, radiotherapy can be proposed associated with anticortisol drugs (mitotane), if needed, while waiting for the late effect of radiotherapy. CLINICALLY SILENT ADENOMAS: Non-functional adenomas should be operated. Some propose adjuvant radiotherapy in all cases and others only if residual tissue persists post-operatively.     

Results and prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma

PURPOSE: To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS: The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION: Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.     

The case-control study as data missing by design: estimating risk differences

OBJECTIVE: To determine the DNA content and S-phase fraction (SPF) of pituitary adenomas by image analysis and to correlate them with clinical and morphologic parameters. STUDY DESIGN: The study group consisted of 26 prospectively collected cases of operated pituitary adenomas (3 microadenomas and 23 macroadenomas). The tumors were classified by histology, immunocytochemistry and electron microscopy. DNA measurement was performed on imprints from fresh pituitary tissue. Samples of nontumorous adenohypophysial parenchyma served as normal controls. RESULTS: Overall, 31% of adenomas, all but one functioning one, were aneuploid. The remaining nonfunctioning aneuploid tumor was a null cell adenoma with glycoprotein differentiation. All aneuploid tumors were macroadenomas, mostly at advanced stages, III and IV. Dural invasion, although frequent in macroadenomas (78%), was not correlated with DNA ploidy and SPF. An increased number of hyperpentaploid aneuploid cells was noted primarily in aneuploid tumors. The mean SPF was < 2.50%, with a statistically significant difference between aneuploid and diploid adenomas (3.60% vs. 1.70%). CONCLUSION: The results suggest that quantitative assessment of DNA content may provide important information, particularly in functioning adenomas. In addition, fresh tissue imprints represent excellent material for optimum cytometric measurements by image analysis systems, even for microadenomas.     

Nonnasopharyngeal lymphoepithelioma of the head and neck

BACKGROUND: Lymphoepithelioma (squamous cell carcinoma with associated lymphoid stroma) commonly occurs in the nasopharynx, rarely at other sites. As a result, the clinical course and optimal treatment of nonnasopharyngeal lymphoepithelioma of the head and neck have not been well described. This retrospective study was undertaken to analyze the clinical course of the disease in patients treated at a single institution and to formulate recommendations for treatment based on that experience as well as results reported in the literature. METHODS: Between 1950 and 1994, 34 patients with nonnasopharyngeal lymphoepithelioma of the head and neck were treated at the University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed and their pathologic specimens evaluated. The primary tumor sites were: oropharynx (24 patients), salivary gland (4), laryngohypopharynx (4), and the maxillary sinus/nasal cavity (2). Assessed in accordance with the 1992 American Joint Committee Against Cancer TNM staging system, T classifications were TX-2, T1-7, T2-8, T3-10, and T4-7, and N classifications were N0-8, N1-5, N2-15, and N3-6. Treatment consisted of radiotherapy for 24 patients, excisional biopsy of the primary tumor followed by radiotherapy for 7 patients, and surgery for 3 patients. Of the patients treated with radiotherapy, neck dissections were performed on only two, both of whom had persistent lymph node masses after completing radiotherapy. The median dose delivered to the primary tumor was 65 gray (Gy) (range, 46-78 Gy). The median fraction size was 2.1 Gy (range, 1.6-3.2 Gy). RESULTS: The 5-year actuarial disease specific survival and overall survival rates were 59% and 39%, respectively. The 5-year actuarial local control rate for all patients was 94%. For the irradiated patients, the 5-year regional control rates were 77% overall and 83% within the radiation field. The 5-year actuarial rate of distant metastasis for all patients was 30%. For patients who presented with and without regional adenopathy, the 5-year rates of distant metastasis were 36% and 12%, respectively (P = 0.27). CONCLUSIONS: Nonnasopharygeal lymphoepithelioma is a radiosensitive disease. High rates of locoregional tumor control were achieved with radiotherapy at all head and neck sites. The main cause of treatment failure was distant metastasis, which occurred more frequently in patients with lymph node involvement. Radiotherapy is appropriate initial locoregional therapy for patients with this disease. Surgery should be reserved for patients who have persistent disease after completing radiotherapy. Systemic therapy is a reasonable approach for patients who present with regional adenopathy because they have a relatively high rate of distant metastasis.     

Flow cytometric analysis of peripheral blood and bone marrow for tumor cells in patients with neuroblastoma

PURPOSE: To report initial clinical experience with a novel high-precision stereotactic radiotherapy system. METHODS AND MATERIALS: Sixty patients ranging in age from 2 to 82 years received a total of 1426 treatments with the University of Florida frameless stereotactic radiotherapy system. Of the total, 39 (65%) were treated with stereotactic radiotherapy (SRT) alone, and 21 (35%) received SRT as a component of radiotherapy. Pathologic diagnoses included meningiomas (15 patients), low-grade astrocytomas (11 patients), germinomas (9 patients), and craniopharyngiomas (5 patients). The technique was used as means of dose escalation in 11 patients (18%) with aggressive tumors. Treatment reproducibility was measured by comparing bite plate positioning registered by infrared light-emitting diodes (IRLEDs) with the stereotactic radiosurgery reference system, and with measurements from each treatment arc for the 1426 daily treatments (5808 positions). We chose 0.3 mm vector translation error and 0.3 degrees rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS: With a mean follow-up of 11 months, 3 patients had recurrence of malignant disease. Acute side effects were minimal. Of 11 patients with low grade astrocytomas, 4 (36%) had cerebral edema and increased enhancement on MR scans in the first year, and 2 required steroids. All had resolution and marked tumor involution on follow-up imaging. Bite plate reproducibility was as follows. Translational errors: anterior-posterior, 0.01 +/- 0.10; lateral, 0.02 +/- 0.07; axial, 0.01 +/- 0.10. Rotational errors (degrees): anterior-posterior, 0.00 +/- 0.03; lateral, 0.00 +/- 0.06; axial, 0.01 +/- 0.04. No patient treatment was delivered beyond the maximum tolerated misalignment. Daily treatment was delivered in approximately 15 min per patient. CONCLUSION: Our initial experience with stereotactic radiotherapy using the infrared camera guidance system was good. Patient selection and treatment strategies are evolving rapidly. Treatment accuracy was the best reported, and the treatment approach was practical.     

Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study

PURPOSE: A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION: Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.     

Zamifenacin (UK-76, 654) a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

PURPOSE: Retrospective studies suggest that prolonged treatment time adversely affects control rates of squamous carcinomas managed by radiotherapy. From 1989 to 1994 a prospective clinical trial was conducted to assess the feasibility and efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy for advanced uterine cervical carcinoma. METHODS AND MATERIALS: Twenty newly diagnosed patients with FIGO stage III squamous cell carcinoma of the cervix were irradiated using a CBASF regimen. Patients received 45 Gy administered to the whole pelvis in 25 fractions in 5 weeks. On Monday, Wednesday, and Friday of the last 3 weeks, an additional 1.6 Gy boost was given 6 hours after the whole pelvis treatment. The 9 boost treatments, totaling 14.4 Gy, were given via lateral fields encompassing the parametria and primary tumor for a cumulative tumor dose of 59.4 Gy. A single low-dose rate brachytherapy procedure was performed within 1 week after the external beam radiotherapy to raise the point A dose to 85-90 Gy in 42 days. Primary endpoints of analysis were local control, complications, and patterns of failure. Results are compared with the outcomes of 21 patients treated with conventionally fractionated (CF) radiotherapy during the same years. RESULTS: Median total treatment time was 46 days in the CBASF group (range 37-62). Median follow-up interval among surviving CBASF patients is 3.8 years. The four-year actuarial local control rates are 78% and 70% in the CBASF and CF groups, respectively (p = ns). Only 2 CBASF patients required a treatment break because of acute toxicity, but severe late complications occurred in 8/20 CBASF patients for a crude rate of 40%. Distant failure was more common than local failure in the CBASF group, and para-aortic node failure occurred in six of the eight CBASF patients with distant failure. CONCLUSIONS: In the management of stage III cervix cancer, the CBASF regimen produced a trend toward improved local control when compared with the CF regimen, shifting the patterns of failure toward a higher rate of isolated distant failures. The high frequency of para-aortic node failure warrants consideration of elective treatment to this region in stage III patients treated with curative intent. Although the high local control rate of the CBASF regimen supports further investigation of accelerated treatment regimens for locally advanced cervix cancer, the unacceptable risk of late complications necessitates refinement in technique and scheduling to improve the therapeutic ratio.     

Combined therapy for primary central nervous system lymphoma in immunocompetent patients

A retrospective series of 13 immunocompetent patients with histological diagnosis of primary central nervous system lymphoma (PCNSL) is presented. The series was divided into Group A, 6 patients treated with radiotherapy alone, and Group B, 7 patients treated with chemotherapy and radiotherapy. Clinicopathological patterns were similar for the two groups. In Group A, 4 patients achieved complete remission after radiotherapy (45-59.4 Gy) but relapsed within 9 months and died within 21 months of diagnosis. 4 Group B patients received chemotherapy followed by radiotherapy, and three who received a methotrexate-containing regimen are alive and disease-free at 34, 42 and 45 months, while the fourth died after 11 months. The other 3 subjects in this group were treated with radiotherapy followed by chemotherapy, and died within 15 months of diagnosis. Although radiotherapy is the standard treatment, chemotherapy has potentially an important role in the management of PCNSL. The sequence of combined treatment could be crucial to improvement of outcome.     

Influence of radiotherapy on long-term relapse in clinically non-secreting pituitary adenomas. A retrospective study (1970-1988)

OBJECTIVE: We wished to evaluate the influence of postoperative radiotherapy on the incidence of tumour regrowth in non-secreting pituitary adenomas. METHODS: The cases of 57 patients with clinically non-secreting pituitary adenomas were retained for a retrospective study of long-term disease-free survival out of a series of 66 patients treated between 1970 and 1988. Thirty-three patients were treated by surgery only (Group A), and twenty-four by surgery followed by external radiotherapy (Group B). Disease-free survival curves were calculated according to the Kaplan-Meyer method and compared by the Logrank test. The impact of some supposed prognostic parameters--such as tumoural volume, macroscopic features of invasiveness and quality of surgical resection--on the disease-free survival was analyzed according to the Logrank adjusted test. RESULTS: The mean follow-up duration was 7.1 +/- 6.2 years, and eleven patients relapsed: nine in group A (27.0%) and two in group B (8.3%), with respective free intervals of 6.1 +/- 5.0 years and 9.6 +/- 2.4 years. Statistical analysis of the disease-free survival curves confirmed that this difference was significant (p < 0.01). Further analysis of putative risk factors (the importance of extrasellar extension and the estimated quality of surgical resection) was attempted, but it did not reach statistical significance. CONCLUSIONS: Radiotherapy is effective in preventing post-operative regrowth of non-secreting pituitary adenomas. Whether it should be systematically proposed or reserved to selected cases remains to be evaluated.     

Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection

PURPOSE: The effect of the sensitizer razoxane on soft tissue sarcomas (STS) was prospectively evaluated in a randomized, controlled trial. The main purpose of the study was to determine the response rates and local control under the combined treatment compared to irradiation alone. METHODS AND MATERIALS: Between 1978 and 1988, 144 patients entered the study; 130 were evaluable for response, toxicity, or survival. The patients were randomized to receive radiotherapy alone or radiotherapy with razoxane. They were divided into postoperative cases and patients with gross disease (unresectable primaries, recurrent disease, or metastatic disease). The median radiation dose was 60 Gy postoperatively, and 56-58 Gy in patients with gross disease. The dose difference has palliative reasons. Razoxane was given orally at a daily dose of 150 mg/m2 during the time of the radiotherapy, starting 5 days before the first irradiation. In general, the groups were comparable as to their prognostic factors. There was some imbalance, however, in favor of the postoperative group reveiving radiotherapy alone. RESULTS: Between the patient groups treated postoperatively in an adjuvant form, there were no substantial differences in local control and survival. Among 82 patients with gross disease, the treatment with radiotherapy and razoxane led to an increased response rate compared to photon irradiation alone (74 vs. 49%). The local control rate was likewise improved (64 vs. 30%;p < 0.05). The acute toxicity was somewhat higher in the sensitizer arm, but there was no difference in the occurrence of late complications. CONCLUSIONS: Radiotherapy combined with razoxane seems to improve the local control in inoperable, residual, or recurrent STS compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary STS or gross disease after incomplete resection, conditions which are still associated with limited local control and a grave prognosis.     

Two-dimensional electrophoresis southern transfer method for detecting human genome variability using a LINE-1 sequence probe

BACKGROUND: Because of a tendency for diffuse, clinically undetectable local spread, cutaneous angiosarcoma is difficult to treat with surgery alone. Radiation is a rational treatment modality for this disease, because a wide region of dermis can be treated, whereas the underlying normal tissues are spared. METHODS: The authors retrospectively studied 14 patients with dermal angiosarcoma of the head and neck who were treated with electron-beam radiation from 1970 to 1989. Primary tumors were located in the scalp and forehead (11 patients) and in the upper face (3 patients). Eleven patients presented with multiple foci of disease. Three patients were treated with radiotherapy alone; the other 11 were treated with chemotherapy (10 patients) and/or surgery (7 patients). Surgical excisions were limited procedures for patients whose disease readily could be encompassed; total scalp resections were not performed. Patients were irradiated with a multiple-field electron-beam technique. Six patients presented postoperatively for radiotherapy with no macroscopic disease in the treatment field and were given a median dose of 60 Gy (range, 50-66 Gy) over a median of 40 days (range, 37-43 days). Eight patients were irradiated with clinically evident disease; doses ranged from 55 to 75 Gy over a median of 44 days (range, 33-66 days). RESULTS: Five of the six patients irradiated without clinically detectable disease were controlled in the treatment field, but only two are currently disease free. Of the eight patients irradiated with macroscopic tumor, initial disease recurrence occurred in the radiation field in two patients and at the radiation field margin in three patients. The actuarial 5-year control rates above the clavicles for patients irradiated with and without clinical disease were 24% and 40%, respectively (P = 0.03). The 5-year actuarial incidence of distant metastases for all patients was 63%. The 5-year actuarial survival rate for patients irradiated with and without clinical disease was 13% and 50%, respectively (P = .04). CONCLUSIONS: Radiation is an effective modality for treating local disease, especially when used after surgical resection of macroscopic tumor. Our current strategy is to resect clinically evident tumor in patients presenting with focal, limited disease, and to follow this resection with moderate dose, very wide-field radiation. The survival outcome for patients presenting with diffuse multifocal disease is bleak, but some patients can be controlled infield with radiation. There must be continued efforts to develop effective systemic therapy.