Reduced-intensity conditioning using fludarabine with either antithymocyte globulin and BU, or low-dose TBI allowing allogeneic hematopoietic SCT.

In a single-center study, we analyzed the outcomes of 66 patients with advanced hematological malignancies receiving two reduced-intensity conditioning regimens for allogeneic transplantation: fludarabine and low-dose TBI (flu/TBI, n=25), or fludarabine, antithymocyte globulin and BU (flu/ATG/BU, n=41). The selection criteria were based on the hypothesis that flu/TBI patients were expected to achieve autologous recovery in the event of non-engraftment. Sixty-three patients (95%) engrafted. Regimen-related mortality at day 100 and 1 year was 6 and 15%, respectively. With median follow-up of 50.4 months, survival did not differ by regimen. Multivariate analysis confirmed that the type of regimen did not affect relapse. In patients achieving full donor chimerism by day 30, those conditioned with flu/TBI showed greater overall survival (P=0.02). Engraftment failure occurred in two patients (3%), both of whom received flu/TBI. We conclude that conditioning with flu/TBI or flu/ATG/BU yields comparable survival and remission outcomes. By contrast to our hypothesis, patients receiving flu/TBI who subsequently failed engraftment did not achieve autologous recovery. Yet, rapid attainment of full donor chimerism after flu/TBI is associated with greater survival than after flu/ATG/BU. Further, larger prospective randomized studies are required to define the advantage of one regimen over the other.

Radiotherapy and radiosurgery for skull base tumors.

Tumors arising in the vicinity of the skull base are relatively uncommon; however, lesions that may be successfully treated by radiotherapy and radiosurgery include temporal bone chemodectomas, schwannomas, juvenile angiofibromas, pituitary adenomas, and meningiomas. This article reviews treatment techniques and results and discusses the pertinent literature.

Radiotherapy alone for clinical T4 skin carcinoma of the head and neck with surgery reserved for salvage.

PURPOSE: To evaluate the outcomes of definitive radiotherapy in the treatment of clinical stage T4 cutaneous carcinomas of the head and neck. PATIENTS AND METHODS: Between October 1964 and September 1997, 85 patients with 88 biopsy-proven clinical AJCC stage T4 carcinomas of the skin of the head and neck received radiotherapy with curative intent. A total of 43 lesions were previously untreated, and 45 were recurrent after other treatment modalities. Histologic types of carcinoma included squamous cell (37 lesions), basal cell (41 lesions), and metatypical basal (basosquamous) cell (10 lesions). Minimum follow-up was 2 years. The product-limit method was used to determine the rates of disease control, severe late complications, and survival. Multivariate analyses included histology, previous treatment, involvement of bone or nerve, number of structures invaded, node stage, external beam dose, and overall treatment time. RESULTS: At 5 years, the rates of local control after radiotherapy and ultimate local control after salvage surgery were 53% and 90%, respectively. Local control rates were better for patients having previously untreated lesions (P =.05). Regional and ultimate regional control rates were 93% and 100%, respectively, and were better for previously untreated lesions (P <.01), basal cell histology or its metatypical variant (P =.04), and absence of bone invasion (P =.08). At 5 years, the risk of severe late complications was 17%, the risk of distant metastasis was 5%, and the overall absolute and cause-specific survival probabilities were 56% and 76%, respectively. CONCLUSION: Radiotherapy alone results in a relatively high probability of cure for selected patients with T4 skin cancers.

Planned postradiotherapy bilateral neck dissection for head and neck cancer.

PURPOSE: This is a retrospective analysis of 50 patients with squamous cell carcinoma of the head and neck treated with radiotherapy (RT) to the primary site and bilateral neck followed by a planned bilateral neck dissection approximately 4 to 6 weeks after completion of RT. PATIENTS AND METHODS: Between November 1964 and March 1997, 50 patients underwent bilateral neck dissections after RT, with minimum 2-year follow-up. Forty-eight patients had bilateral positive neck nodes. RESULTS: At 5 years, the rates of neck disease control, local-regional control, and cause-specific survival were 76%, 70%, and 39%, respectively. Five severe complications developed after surgery, and 1 developed after RT. CONCLUSIONS: Radiotherapy followed by a planned bilateral neck dissection resulted in a high rate of local-regional control with acceptable morbidity. The likelihood of severe complications after simultaneous (as opposed to staged) neck dissection was not significantly different (P =.24).

An algorithm for evaluating the ethics of a placebo-controlled trial.

The purpose of this article is to clarify the decision points that are important to consider when evaluating the ethics of a placebo-controlled trial. The ethical requirements for research involving human subjects are reviewed, and the rationale for and potential problems with concomitant placebo control are explained. A series of case discussions are used to illustrate each decision point. The critical decision points in the evaluation of the ethics of a placebo-controlled trial are as follows: (i) Is placebo being used in place of standard therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity of standard therapy such that patients routinely refuse this treatment? (iv) Could the use of placebo result in severe suffering or irreversible harm? (v) Is the variability in the placebo response such that it is reasonable to consider other options for the control group? (vi) Would a reasonable person with an average degree of altruism and risk aversiveness agree to participate in this study? The algorithm presented in this article gives researchers and research monitors (such as Institutional Review Board members) the tools they need to evaluate the ethics of a study that uses concomitant placebo control.

T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy.

PURPOSE: The end results after radiation therapy for T1-T2N0 glottic carcinoma vary considerably. We analyze patient-related and treatment-related parameters that may influence the likelihood of cure. PATIENTS AND METHODS: Five hundred nineteen patients were treated with radiation therapy and had follow-up for >or= 2 years. Three patients who were disease-free were lost to follow-up at 7 months, 21 months, and 10.5 years. No other patients were lost to follow-up. RESULTS: Local control rates at 5 years after radiation therapy were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 72%. Multivariate analysis of local control revealed that the following parameters significantly influenced this end point: overall treatment time (P < .0001), T stage (P = .0003), and histologic differentiation (P = .013). Patients with poorly differentiated cancers fared less well than those with better differentiated lesions. Rates of local control with laryngeal preservation at 5 years were as follows: T1A and T1B, 95%; T2A, 82%; and T2B, 76%. Cause-specific survival rates at 5 years were as follows: T1A and T1B, 98%; T2A, 95%; and T2B, 90%. One patient with a T1N0 cancer and three patients with T2N0 lesions experienced severe late radiation complications. CONCLUSION: Radiation therapy cures a high percentage of patients with T1-T2N0 glottic carcinomas and has a low rate of severe complications. The major treatment-related parameter that influences the likelihood of cure is overall treatment time.

Treatment of paragangliomas with radiation therapy.

Paragangliomas of the head and neck may be treated successfully with surgery, radiation therapy, or stereotactic radiosurgery. The choice of treatment depends on the location and extent of the tumor, the presence of multiple tumors, the age and health of the patient, and the preference of the patient and attending physician. This article reviews the role of radiation therapy in the treatment of patients with paragangliomas of the head and neck.

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site.

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site is relatively uncommon and presents a challenging diagnostic and therapeutic dilemma. Diagnostic evaluation includes fine-needle aspiration of the neck mass, chest roentgenography, computed tomography, and/or magnetic resonance imaging of the head and neck, followed by panendoscopy and biopsies. The primary tumor will be detected in approximately 40% of patients; approximately 80% of cancers are located in the base of the tongue or tonsillar fossa. Management options include treatment of the neck alone or both sides of the neck and the potential head and neck primary sites. The latter approach is associated with better long-term control above the clavicles. The 5-year survival rate is approximately 50% after treatment and is influenced by the extent of neck disease. In this article, we review the pertinent literature.

Long-term results of radiation therapy for juvenile nasopharyngeal angiofibroma.

PURPOSE: To analyze 15 patients treated with radiation therapy for juvenile nasopharyngeal angiofibroma (JNA) between June 1975 and March 1996. MATERIALS AND METHODS: All patients had a 2.5-year minimum follow-up. All patients had advanced disease (Chandler stage III or stage IV); two thirds of the patients had intracranial extension. RESULTS: Local control after radiotherapy was obtained in 13 of 15 patients (85%). Two patients had local recurrences, and both were salvaged with surgery for an ultimate local control rate of 100%. Late complications included cataracts in 3 patients, delayed transient central nervous system (CNS) syndrome in 1 patient, and a basal cell carcinoma of the skin in 1 patient. Of 15 patients, 13 (85%) had a complete response (CR) on physical examination following radiation therapy. The median time to CR was 13 months (range, 1 to 39 months). Of 6 patients with residual disease in more than 24 months, 2 (33%) had a recurrence, whereas no patient achieving CR in less than 24 months experienced a recurrence. CONCLUSIONS: Radiotherapy is an effective treatment for advanced JNA. Tumor regression usually occurs slowly over several months. JNAs that are slow to regress (greater than 2 years) may have an increased risk of recurrence.

Squamous cell carcinomas of the soft palate treated with radiation therapy alone or followed by planned neck dissection.

PURPOSE: The present study presents the experience at the University of Florida with treatment of unselected patients with carcinomas of the soft palate with radiation therapy (RT) alone or followed by planned neck dissection. METHODS AND MATERIALS: One hundred seven patients treated with curative intent with RT alone or followed by neck dissection from 1965 to 1996 were included in the study. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: Local control rates at 5 years were 86% for T1, 91% for T2, 67% for T3, and 36% for T4 carcinomas. T-stage and overall treatment time significantly affected local control in multivariate analysis. Nodal control rates at 5 years were 86% for NO, 76% for N1, 61% for N2, and 67% for N3 carcinomas. Overall treatment time and planned neck dissection significantly affected nodal control in multivariate analysis. Ultimate local-regional control rates at 5 years were 90% for Stage I, 92% for Stage II, 84% for Stage III, and 60% for Stage IV disease. Overall treatment time and planned neck dissection significantly affected ultimate local-regional control in multivariate analysis. The overall survival rate at 5 years was 42% for all patients. Overall stage, overall treatment time, and planned neck dissection significantly affected overall survival in multivariate analysis. The cause-specific survival rate at 5 years was 70% for all patients. Overall treatment time and planned neck dissection significantly affected cause-specific survival in multivariate analysis. Three patients sustained severe postoperative complications and 3 patients sustained severe late complications. Sixteen patients had synchronous and 14 patients had metachronous carcinomas of the head and neck mucosal sites. CONCLUSION: For limited carcinomas of the soft palate, RT (alone or followed by planned neck dissection) results in relatively high local-regional control and survival rates. For advanced carcinomas of the soft palate, local-regional control and survival rates are relatively low and local-regional recurrence rates are substantial. Advanced carcinomas of the soft palate may be better treated with RT and concomitant chemotherapy.

Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck mucosal site treated with radiation therapy with palliative intent.

Minimal information has been published about the results of palliative irradiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Forty patients with this diagnosis were treated at the University of Florida with radiation therapy with palliative intent. The nodal response rate was 65% and the symptomatic response rate was 57% at 1 year. The absolute survival rate was 25% at 1 year, as was the cause-specific survival rate. Radiotherapy successfully palliates more than half of those treated. Approximately one fourth are alive 1 year after irradiation.

Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection.

PURPOSE: The present study presents the experience at the University of Florida with treatment of patients with squamous cell carcinomas (SCC) metastatic to cervical lymph nodes from an unknown head-and-neck mucosal (H&NM) site with radiotherapy (RT) alone or in combination with neck dissection (ND). METHODS AND MATERIALS: The study included 126 patients treated with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: Twelve patients (10%) developed SCC in H&NM sites at 0.5 to 10.9 years (median, 1.8 years). The rate of developing carcinomas in H&NM sites at 5 years was 13%. Histologic differentiation significantly affected the rate of developing carcinomas in H&NM sites in multivariate analysis. Sixteen patients (13%) had persistent nodal disease and 12 patients (10%) developed recurrent nodal disease at 0.5 to 10.9 years (median, 1.1 years). The nodal control rate at 5 years was 78%. Nodal size, N stage, and planned ND significantly affected the rate of nodal control in multivariate analysis. Nineteen patients (15%) developed distant metastasis at 0.2-5.1 years (median, 0.9 years). The distant metastases rate at 5 years was 14%. Extracapsular extension and RT dose significantly affected the risk of distant metastases in multivariate analysis. The overall absolute survival rate at 5 years was 47%. Extracapsular extension, N stage, RT dose for H&NM sites, and planned ND significantly affected absolute survival in multivariate analysis. The rate of cause-specific survival at 5 years was 67%. Extracapsular extension, nodal size, N stage, overall treatment time, and planned ND significantly affected cause-specific survival in multivariate analysis. Eight patients (6%) had severe postoperative complications and 6 patients (5%) had severe late complications. CONCLUSION: The present study supports the effectiveness of RT in lowering the rate of developing carcinomas in the H&NM sites.

Definitive radiotherapy in the management of chemodectomas arising in the temporal bone, carotid body, and glomus vagale.

PURPOSE: To evaluate the results of treatment for 71 patients with 80 chemodectomas of the temporal bone, carotid body, or glomus vagale who were treated with radiation therapy (RT) alone (72 tumors in 71 patients) or subtotal resection and RT (8 tumors) at the University of Florida between 1968 and 1998. METHODS AND MATERIALS: Sixty-six lesions were previously untreated, whereas 14 had undergone prior treatment (surgery, 11 lesions; RT, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All three patients who received prior RT had been treated at other institutions. Patients had minimum follow-up times as follows: 2 years, 66 patients (93%); 5 years, 53 patients (75%); 10 years, 37 patients (52%); 15 years, 29 patients (41%); 20 years, 18 patients (25%); 25 years, 12 patients (17%); and 30 years, 4 patients (6%). RESULTS: There were five local recurrences at 2.6 years, 4.6 years, 5.3 years, 8.3 years, and 18.8 years, respectively. Four were in glomus jugulare tumors and one was a carotid body tumor. Two of the four patients with glomus jugulare failures were salvaged, one with stereotactic radiosurgery and one with surgery and postoperative RT at another institution. Two of the five recurrences had been treated previously at other institutions with RT and/or surgery. Treatment for a third recurrence was discontinued, against medical advice, before receiving the prescribed dose. There were, therefore, only 2 failures in 65 previously untreated lesions receiving the prescribed course of RT. The overall crude local control rate for all 80 lesions was 94%, with an ultimate local control rate of 96% after salvage treatment. The incidence of treatment-related complications was low. CONCLUSIONS: Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone and neck. There were no severe treatment complications.

Organ preservation with radiotherapy for T1-T2 carcinoma of the pyriform sinus.

PURPOSE: To report long-term results using radiotherapy with or without a planned neck dissection for T1-T2 carcinoma of the pyriform sinus. METHODS: An analysis of 101 patients treated at the University of Florida with RT with or without a planned neck dissection for organ preservation. RESULTS: The 5-year local control rates after RT were 90% for T1 cancers and 80% for T2 lesions. The only parameter that significantly influenced local control in univariate analyses was apex involvement for T1 tumors. Multivariate analysis revealed no parameter that significantly affected local control. Cause-specific survival rates at 5 years were as follows: stage I-II, 96%; stage III, 62%; stage IVA, 49%; and stage IVB, 33%. The absolute survival rates were as follows: stage I, 57%; stage II, 61%; stage III, 41%; stage IVA, 29%; and stage IVB, 25%. Moderate to severe long-term complications developed in 12% of patients. CONCLUSIONS: RT alone or combined with a planned neck dissection resulted in local control with larynx preservation in a high proportion of patients. The chance of cure is comparable to that observed after conservation surgery, and the risk of major complications is lower. The addition of adjuvant chemotherapy is unlikely to improve the probability of organ preservation, but might improve locoregional control for patients with advanced nodal disease.

Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites.

PURPOSE: The present study presents the experience at the University of Florida with synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. PATIENTS AND METHODS: This study included 1,112 patients with squamous cell carcinomas of the oropharynx, hypopharynx, and supraglottic larynx treated with radiation therapy with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: The overall survival rate was 45% and the disease-specific survival rate was 67% at 5 years after initial diagnosis of carcinoma of the head and neck mucosal sites. Seventy-seven patients (7%) presented with synchronous carcinomas of the head and neck mucosal sites and 103 patients (9%) developed metachronous carcinomas of the head and neck mucosal sites at 0.6 to 21.7 years (median, 3.6 years). The overall survival rate was 31%, and the disease-specific survival rate was 50% at 5 years after metachronous carcinomas of the head and neck mucosal sites. Seven patients (1%) developed metachronous carcinomas of the thoracic esophagus at 1 to 11.1 years (median, 2.8 years), 15 patients (1%) presented with synchronous carcinomas of the lung, and 83 patients (7%) developed metachronous carcinomas of the lung at 0.6 to 17.6 years (median, 3.5 years). CONCLUSION: Development of synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites are in part responsible for failure to improve overall survival rates for patients with squamous cell carcinomas of the head and neck mucosal sites, justifying rigorous follow-up and studies on chemoprevention.

Patterns of failure in squamous cell carcinoma of the vagina treated with definitive radiotherapy alone: what is the appropriate treatment volume?

The purpose of this study was to review treatment results, sites of failure, and complications in relation to the irradiation volume for carcinoma of the vagina treated with radiotherapy alone. A retrospective review of 65 patients with histologically confirmed squamous cell carcinoma of the vagina who received definitive radiotherapy was undertaken. The 5-year cause-specific survival rates were as follows: Stage I, 91%; Stage IIA (paravaginal extension), 90%; Stage IIB, 55%; Stage III, 89%; and Stage IVA, 62%. The pelvic disease control rates at 5 years were as follows: Stage I, 74%; Stage IIA, 90%; Stage IIB, 79%; Stage III, 89%; and Stage IVA, 67%. Recurrence in the pelvis occurred in 22% of patients. Eighty-five percent of pelvis recurrences were in the primary treatment field. Although pelvic control rates were not increased by use of larger treatment fields (>2,700 cm(3)), moderate acute and late effects were increased with these fields. Carcinoma of the vagina appears to have a different failure pattern than carcinoma of the cervix. The primary failure sites are the vagina and the paracolpal tissues and the inguinal nodes. Because of this, the superior edge of the pelvic fields does not have to extend above the bottom of the sacroiliac joints except with advanced lesions.

Radiation therapy for squamous cell carcinoma of the tonsillar region: a preferred alternative to surgery?

PURPOSE: There are no definitive randomized studies that compare radiotherapy (RT) with surgery for tonsillar cancer. The purpose of this study was to evaluate the results of RT alone and RT combined with a planned neck dissection for carcinoma of the tonsillar area and to compare these data with the results of treatment with primary surgery. PATIENTS AND METHODS: Four hundred patients were treated between October 1964 and December 1997 and observed for at least 2 years. One hundred forty-one patients underwent planned neck dissection, and 18 patients received induction (17 patients) or concomitant (one patient) chemotherapy. RESULTS: Five-year local control rates, by tumor stage, were as follows: T1, 83%; T2, 81%; T3, 74%; and T4, 60%. Multivariate analysis revealed that local control was significantly influenced by tumor stage (P =.0001), fractionation schedule (P =.0038), and external beam dose (P =.0227). Local control after RT for early-stage cancers was higher for tonsillar fossa/posterior pillar cancers than for those arising from the anterior tonsillar pillar. Five-year cause-specific survival rates, by disease stage, were as follows: I, 100%; II, 86%; III, 82%; IVa, 63%; and IVb, 22%. Multivariate analysis revealed that cause-specific survival was significantly influenced by overall stage (P =.0001), planned neck dissection (P =.0074), and histologic differentiation (P =.0307). The incidence of severe late complications after treatment was 5%. CONCLUSION: RT alone or combined with a planned neck dissection provides cure rates that are as good as those after surgery and is associated with a lower rate of severe complications.

Altered fractionation in definitive irradiation of squamous cell carcinoma of the head and neck.

The likelihood of local control after radiation therapy may be improved by increasing total dose or decreasing overall time. The probability of late complications increases with dose per fraction. Altered fractionation techniques usually employ two or more fractions per day using a dose per fraction that is similar or less than that employed in conventional fractionation. Altered fractionation may be broadly classified as hyperfractionation or accelerated fractionation. Data suggest that altered fractionation schedules may improve local control (and to a lesser extent, survival) compared with conventional irradiation.