Impact of radiation therapy fraction size on local control of early glottic carcinoma

PURPOSE: Different radiotherapy fractionation schedules were used over a 10-year period to treat patients with early squamous cell carcinoma of the vocal cords at McGill University. A retrospective analysis was performed to study the effect of fraction size on local control in this group of patients. METHODS AND MATERIALS: A total of 126 previously untreated patients with T1 invasive squamous cell carcinoma of the true vocal cords were irradiated between January 1978 and December 1988 in the Department of Radiation Oncology at McGill University. All patients received megavoltage irradiation, 94 patients received daily fractions > 2 Gy (64 patients received 50 Gy with once-daily 2.5-Gy fractions, and 30 received 65.25 Gy in 29 fractions of 2.25 Gy each), and 32 patients were treated to a dose of 66 Gy in 33 fractions with 2 Gy/fraction. Patients' characteristics of prognostic importance were equally distributed between the two fractionation groups. RESULTS: At a median follow-up of 84 months, the 10-year disease-free survival and overall survival were 76% and 93%, respectively. Local control for patients treated with > 2 Gy fraction was 84%, compared to 65.6% for those treated with 2-Gy fractions (p = 0.026). Among the prognostic factors tested, such as gender, age, stage, anterior and posterior commissure involvement, smoking history, and fraction size, the latter was the only significant predictor of local control for the whole group of patients in univariate (p = 0.041) and multivariate (p = 0.023) analysis. There was no observed difference in the incidence of complications between the two fractionation groups. CONCLUSIONS: From the results of this retrospective review of patients treated with radiotherapy for T1 true vocal cord cancer, and within the range of total doses and overall treatment times used in our patients, it was found that fractionation schedules using daily fraction size > 2 Gy are associated with a better local control than schedules delivering 2 Gy/fraction, with no increase in toxicity.     

Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma

BACKGROUND/AIMS: Experimental and clinical studies have found a relationship between blood transfusion and altered immune function. We estimated the risk of transfusions for shorter survival on patients with hepatocellular carcinoma who underwent hepatic resection. METHODOLOGY: The impact of perioperative blood transfusions on 235 patients with hepatocellular carcinoma who had resections from January 1981 to December 1988 was retrospectively examined. All patients underwent hepatic resection and received no additional chemotherapy. RESULTS: Using the Cox proportional hazard model, the number of perioperative blood transfusions was found to be a significant prognostic factor for patient outcome (p = 0.03). Overall, patients who received less than 12 transfused units had a significantly better 5-year survival rate than those who received more than 13 transfused units (46.3% vs. 24.5%, p < 0.001). This result was also seen when the patients were subdivided by stage: 5-year survival in the early stage group (57.2% vs. 35.5%, p < 0.01) and in the advanced stage group (30.0% vs. 18.2%, p < 0.05). The number of perioperative blood transfusions also influenced the survival of patients who underwent a curative resection (66.2% vs. 38.5%, p < 0.01), but did not affect the survival of those who received a non-curative resection (7.9% vs. 7.4%). CONCLUSION: This study suggests that the number of perioperative blood transfusions is a significant prognostic factor in patients with hepatocellular carcinoma who undergo hepatic resection.     

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

Penile cancer in Taiwan--20 years' experience at National Taiwan University Hospital

To analyze the characteristics and prognostic factors of penile cancer in Taiwanese, we retrospectively reviewed the clinical data of patients with a diagnosis of penile cancer treated during a 20-year period (1977-1996) at National Taiwan University Hospital (NTUH). Of 71 patients treated for penile cancer during the study period, 17 were referred from other hospitals or clinics. Our analyses focused on the 54 previously untreated patients. Growth on the penis was the main symptom in all cases. Palpable inguinal lymph nodes were found only in 14 patients. All 54 patients with primary tumors were treated surgically. Pathologic examination showed squamous cell carcinoma (SCC) in 43 cases, extra-mammary Paget's disease in three, verrucous carcinoma in three, Bowen's disease in two, cutaneous lymphoma in two and basal cell carcinoma in one. Twenty-six (48%) patients had stage I penile cancer, 13 (24%) had stage II, seven (13%) had stage III, and eight (15%) had stage IV cancer. The five-year survival rate was 78% among patients with SCC and 84% among those with nonsquamous malignancies (p = 0.80). The five-year cumulative survival rates according to Jackson's cancer stage were 100% for patients with stage I, 88.9% for those with stage II, 66.7% for those with stage III, and 0% for those with stage IV (p < 0.001). Tumor staging (p = 0.027) and adjuvant chemotherapy (p = 0.042) were found to be the most significant prognostic factors. Penile cancer accounted for 0.254% of all malignancies among male patients at the NTUH during the study period. Our findings indicate that penile cancer is uncommon in Taiwanese and its prognosis is closely related to tumor staging and management. Early diagnosis and appropriate treatment may lead to prolonged survival.     

Contrasting effects of an aminobisphosphonate, a potent inhibitor of bone resorption, on lipopolysaccharide-induced production of interleukin-1 and tumour necrosis factor alpha in mice

PURPOSE: To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence. METHODS AND MATERIALS: Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml. RESULTS: At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure. CONCLUSION: This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.     

Disseminated intravascular coagulation: pathophysiology and principles of management

OBJECTIVE: To analyze the survival and the main prognostic factors in patients with transitional cell carcinoma of the upper urinary tract. METHODS: From 1983 to 1996, we treated 50 patients with transitional cell carcinoma of the upper urinary tract. Treatment was basically conservative except in those cases whose tumor stage or grade required a radical approach. Grading and staging were performed according to the 1992 TNM classification. Eighteen patients had died at one year mean follow-up., At the time the study was completed (June, 1997), 32 patients were alive with a mean follow-up of 4.9 years. Disease-free survival, overall and specific survival were analyzed according to sex, age, association with bladder tumors, localization, type of treatment, tumor size, number, histological grade and stage. RESULTS: The male-to-female ratio was 5:1. Patient mean age was 65.7 years. Association with bladder tumors was observed in 50%. Treatment was conservative in 40% and radical in 60%. The five- and ten-year disease-free survival rates were 69%, overall survival 61% and specific survival 71%. The univariate analysis showed the following to be unfavorable prognostic factors for survival: renal vs ureteral tumors, radical vs conservative treatment, high grade and stage tumors. The association of carcinoma in situ with other tumors of the upper urinary tract was also found to be an unfavorable factor for disease-free survival. The multivariate analysis associated T4 and G3 tumors with poor prognosis. CONCLUSIONS: Transitional cell carcinoma of the upper urinary tract was associated with bladder tumors in 50% of the cases. Low grade stage tumors demonstrated a high survival rate, therefore conservative treatment should be the first approach. High grade/ stage tumors were found to be unfavorable prognostic factors for survival.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.     

Optimization of arbitrarily primed polymerase chain reaction (AP-PCR)-based DNA fingerprinting of Mycobacterium tuberculosis and its clinical application

OBJECTIVE: External irradiation is an accepted curative treatment modality for patients with localized prostatic tumor. The 15-year results in patients treated by radical irradiation alone are presented. The determinant prognostic factors for local tumor control and disease free survival are analyzed. METHODS: 135 patients with a histologically confirmed localized carcinoma of the prostate were treated at our department from May 1972 to January 1998. Fifty patients received Co-60 therapy; the linear accelerator and high energy photons were utilized in the remaining 80 patients. By tumor stage, 53 patients were B1, 49 B2 and 33 C. The mean follow-up was 61 months (range 1-180). Most patients were exposed to localized fields of irradiation; dose ranged from 50-74 Gy, fractionated at a dose of 180-200 cGy/day. RESULTS: Overall local tumor control was 77% at 5 years and 73% at 15 years, with a disease free survival of 63% and 45% at 5 and 15 years, respectively. Local tumor control at 13 years was 71% for stage B1, 82% for B2 and 70% for C. The disease free survival at 13 years for stages B1, B2 and C were 46%, 49% and 36%, respectively. The BD and MD tumors had a 15-year disease free survival of 48% vs 32% for the PD tumors (p = 0.005). Patients with PSA < or = 20 ng/ml before treatment showed a disease free survival of 87% vs 48% for those with PSA > 20 ng/ml ((p = 0.011). Multivariate analysis showed dose to be a determinant prognostic factor for local tumor control (0.0432); dose and histological grade were determinants for disease free survival (p = 0.029 and 0.033). CONCLUSIONS: This retrospective study found dose to be a determinant prognostic factor for local tumor control and both dose and histological grade were determinants for disease free survival. Radiotherapy is a therapeutic option for these patients. The results can be enhanced if the dose delivered to the prostate can be increased while maintaining the complication rate within the same ranges.     

The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases

BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively.     

Prognostic factors in radiation-treated esophageal carcinoma

Prognostic factors in esophageal carcinoma treated with irradiation were examined. The prognosis of 111 patients without metastasis who had received more than 60 Gy was analyzed. Significant associations were found between survival rates and tumor length, stage, radioresponse of the primary tumor and the s.c. X-P classification based on barium contrast radiography; superficial type (tumor limited to the surface of the esophageal wall), tumorous type (solid mass without ulceration), Ul-A type (tumor with shallow ulceration with regular margin), Ul-B type (tumor with deep ulceration or irregular ulcer margin), and funneled type (tumor invading the esophageal wall in a scirrhous pattern). In multiple regression analysis, the X-P classification had the strongest correlation with survival and the survival rates of patients with the superficial type, the tumorous type and the s.c. Ul-A type were significantly higher than those of patients with the other tumor types (p < 0.001).     

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.     

Radiotherapy of follicle center lymphoma. Results of a German multicenter and prospective study. Members of the Study Group "NHL-early stages"

PURPOSE: Follicle centre lymphoma grade I, II (REAL) or centroblastic-centrocytic lymphoma (Kiel classification) present a well defined clinical entity from a clinical point of view. These lymphomas are not curable by chemotherapy in early or advanced stages. They are treated by radiation therapy in early stages, but up to now the curative potency of radiotherapy has not been confirmed by prospective clinical trials. PATIENTS AND METHODS: Between January 1986 and August 1993 117 adults with follicle centre lymphoma were recruited from 24 institutions to enter the multicentric prospective, not randomised clinical trial. Patients with histologically proven nodal follicle centre lymphoma of stages I, II and limited III were included. They were treated by a standardised radiotherapy regimen, in stage I by extended field and in stages II and III by total nodal irradiation. Dose per fraction was 1.8 to 2.0 Gy, in the abdominal bath 1.5 Gy up to a total dose of 26 Gy in adjuvant situation and 36 Gy to enlarged lymphoma. RESULTS: All patients developed a complete remission at the end of radiotherapy. Median follow-up is 68 months. Overall survival of all patients in 86 +/- 3% at 5 and 8 years. Stage adjusted survival at 5 and 8 years was 89% for stage I, 86% for stage II and 81% for III. Patients in stages I and II < 60 years had survival rates of 94% at 5 and 8 years, patients > 60 years 63% (p < 0.0001). Recurrence free survival of all patients is 70% at 5 and 60 +/- 5% at 8 years. The number of recurrences is high with 29% at 5 and 41% at 8 years. All recurrences were seen within 7 years. The probability of localised nodal in-field recurrences is 11% and 22% at 5 and 8 years, respectively. Adverse prognostic factors were identified by multivariate analysis: age > 60 years, treatment breaks > or = 7 days and dose deviations > 20% from prescribed doses. Acute side effects of extended field irradiation were moderate. CONCLUSIONS: On the basis of these results radiotherapy is a potentially curative therapeutic approach in stages I, II and limited III of follicle centre lymphoma. The optimal technique is total lymphoid irradiation with doses of 30 Gy in the adjuvant situation and 40 to 44 Gy in enlarged lymphomas. The number of local recurrences leads to the assumption, that the extension of radiotherapy to the total lymphoid system might reduce their frequency.     

What''s new in nail surgery?

BACKGROUND: Inflammatory breast cancer (IBC) is a rare form of rapidly progressive breast cancer. We reviewed the diagnosis, treatment, and outcome of IBC in our inner city community-based hospital and compared results with previous published reports. STUDY DESIGN: Twenty-five patients were diagnosed and treated for IBC at the Catholic Medical Center of Brooklyn and Queens during the 6-year period of January 1989 through December 1995. Criteria for inclusion in this study were clinical or histopathologic evidence, or both, of inflammatory carcinoma. RESULTS: IBC comprised 2.0% (25 of 1,257) of all breast cancer patients initially diagnosed during this study. All presented with clinical signs of IBC. Invasion of dermal lymphatics by neoplastic cells was demonstrated in 68% (17 of 25) of biopsy specimens. Sixty-eight percent (17 of 25) of patients presented with metastatic (ie, stage IV) disease and 28% (7 of 25) with stage IIIb; one patient (4%) died before staging. Estrogen and progesterone receptor studies were done on 72% (18 of 25) of all specimens. Of those patients who died, 85% were estrogen and progesterone receptor negative; of those surviving, 60% were estrogen receptor positive. Twenty (80%) of the 25 patients died, after a mean survival of 11.8 months and 5 (20%) remain alive, with a mean survival of 44.8 months. Of those who died, 85% were stage IV at presentation. All five survivors were stage IIIb at presentation. Patients underwent a variety of multimodal therapies. Survival was significantly associated with earlier stage at diagnosis and estrogen receptor positivity. CONCLUSIONS: IBC is characterized by rapid progression and dismal outcome. Earlier stage at diagnosis and positive estrogen receptor status suggest a more favorable prognosis. Neoadjuvant chemotherapy, as part of a multimodal approach, has significantly improved the outcome for IBC, but this is limited to patients with stage IIIb disease. Most of our patients presented with stage IV disease. If improvement is to be realized at the community level, limited health care resources must be directed toward aggressive physician and public education.     

Treatment outcome with radiation therapy after breast augmentation or reconstruction in patients with primary breast carcinoma

BACKGROUND: Analyses were performed to determine local control and cosmetic outcome of breast carcinoma patients with prosthetically augmented or reconstructed breasts who had received radiation therapy (RT). METHODS: Twenty-one newly diagnosed breast carcinoma patients with prosthetically augmented or reconstructed breasts were treated with external beam RT. All patients received whole breast RT (median dose, 50.4 gray [Gy]) and 19 were boosted to a median dose of 60.4 Gy. A median dose of 50.4 Gy was delivered to the regional lymph nodes in 12 patients. Tissue equivalent bolus material was used in six patients. Seventeen patients received adjuvant systemic therapy. Cosmetic results were evaluated at 3-6-month intervals. RESULTS: With a median follow-up of 32 months, good/excellent cosmetic results were observed in 71% of patients (100% in those with augmented breasts and 54% in those with reconstructed breasts). Four patients (19%) with fair/poor cosmetic outcomes required implant removal and/or revision. Multiple clinical and treatment-related factors were analyzed for their impact on cosmetic outcome. A worsened cosmetic result was observed with increasing stage (P = 0.076), breast reconstruction (vs. augmentation) (P = 0.030), and bolus application (P = 0.016). All patients with fair/poor cosmetic outcomes had time intervals from implant insertion to RT ranging from 53-213 days. Two patients developed an isolated local recurrence within the augmented breast. CONCLUSIONS: Patients with prosthetically augmented breasts can undergo RT and expect good/excellent cosmetic results. Patients with reconstructed breasts are at a significantly greater risk for cosmetic failure. This risk may be related to the higher percentage of patients with advanced disease, those who received bolus application, and those who received earlier delivery of RT (after the cosmetic procedure) in reconstructed breasts.     

Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis

BACKGROUND: Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. METHODS: The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. RESULTS: The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age < or =60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors < or =5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. CONCLUSIONS: Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.     

Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians

Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.     

Comparison of tethered star and linear poly(ethylene oxide) for control of biomaterials surface properties

BACKGROUND: Breast carcinoma in males is infrequent, and information regarding the results of modern treatment is limited. Cases of breast carcinoma in males were accrued from multiple hospitals in one region to determine treatment, survival, and prognostic factors. METHODS: A retrospective review was performed of 217 cases of breast carcinoma in males accessioned at tumor registries of 18 health care institutions in eastern Wisconsin between 1953 and 1995. RESULTS: Of the 217 cases, 215 (99.1%) were carcinomas. The majority of carcinomas were of invasive ductal type and presented as masses. Carcinoma in situ accounted for 5.5% of cases. The 5- and 10-year observed survivals for men were 50.6% and 23.7%, respectively. A high rate of post-treatment mortality from comorbid disease was found. Stage, axillary lymph node status, number of lymph nodes with metastases, and tumor hormone receptors were significant indicators of prognosis. Adjuvant systemic chemotherapy and hormone therapy improved the prognosis of patients with axillary lymph node metastases and hormone receptor positive tumors. Earlier stage at presentation and improved 5-year survival were found in cases occurring between 1986-1995 compared with those occurring in earlier years. Use of modified radical mastectomy and systemic adjuvant therapy also increased since 1986. CONCLUSIONS: The clinical, pathologic, and prognostic features of breast carcinoma in men are similar to those reported for women. The poorer prognosis of men is related to older age at diagnosis, more advanced stage of disease at presentation, and high mortality from comorbid disease. Earlier diagnosis, less radical surgery, and use of systemic adjuvant therapy are coincident with an improved prognosis for men.     

Carcinoma of the nasopharynx in young patients

PURPOSE: To provide an analysis of eighteen cases of adolescent nasopharyngeal carcinoma treated between 1971 and 1989. METHODS AND MATERIALS: Between 1971 and 1989, 48 cases of nasopharyngeal carcinoma were evaluated at the Medical College of Georgia Hospital and Clinics. Eighteen patients between the ages of 9 and 29 years were treated at the Georgia Radiation Therapy Center. All patients presented for treatment with (AJCC) Stage IV disease. Fifteen patients with lymphoepithelioma and three with squamous cell carcinoma histologies received definitive radiation therapy to a median dose of 64.8 Gy. Males outnumbered females by more than 2:1 and the majority of patients (67%) were black. Nine patients received multiagent adjuvant chemotherapy. RESULTS: Thirteen patients are alive from 7 to 166 months (median 32 months) including three with disease at 17, 24, and 132 months. Overall and disease-free survival at 5 and 10 years were 63% and 54%, respectively. Five patients died from disease; four patients had pulmonary metastases while one had CNS metastasis. Eighty percent of relapses occurred within the first 2 years following treatment. Acute and chronic toxicities were limited, consisting primarily of mucositis and xerostomia. Radiation doses of 65 Gy or more (p = 0.049) and age greater than 20 years (p = 0.005) were positive prognosticators for survival. Adjuvant chemotherapy, race, and sex were not found to be of prognostic value. Disparities in the distribution of patients with lymphoepithelioma and squamous cell histologies and the presentation of advanced regional disease precluded analysis for prognostic significance of histology and nodal status in this series. CONCLUSION: The results of the present series compare favorably with those published from other institutions. High doses of radiation and a high systemic failure rate continue to be the fundamental obstacles to effective management and enhanced survival for patients with nasopharyngeal carcinoma.