Impact of involved field radiotherapy after CHOP-based chemotherapy on stage III-IV, intermediate grade and large-cell immunoblastic lymphomas

PURPOSE: To analyze the impact of involved field radiotherapy on local control, freedom from progression, and overall survival in patients with clinical Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based induction chemotherapy. METHODS AND MATERIALS: From July 1989 through October 1996, 32 patients with clinical Stage III and 27 patients with clinical Stage IV, intermediate grade, or large-cell immunoblastic lymphomas were prospectively enrolled on two protocols at The University of Texas M. D. Anderson Cancer Center. None had previously undergone treatment for lymphoma. The median patient age was 54 years (range: 26-85 years). There were a total of 172 involved sites of disease at presentation. All 59 patients received CHOP-based chemotherapy. At least six cycles of chemotherapy were delivered to 92% of the patients. Involved field radiotherapy (39.6-40.0 Gy in 20-22 fractions in 74% of cases) was administered to 28/59 (47%) patients beginning 3-4 weeks after chemotherapy. Sites were irradiated at the discretion of the treating physician. Irradiated and nonirradiated groups were compared in terms of maximum pre-chemotherapy tumor size and University of Texas M. D. Anderson Cancer Center tumor score. Kaplan-Meier estimates of local control per patient, freedom from progression, and overall survival for the irradiated and nonirradiated groups were calculated in terms of the stage of disease and treatment delivered. The resulting curves were compared using the log-rank test. The Cox proportional hazards model was used to assess the prognostic significance of tumor size, tumor score, treatment delivered, and stage. RESULTS: The median length of follow-up for all patients was 53 months (range: 4-96 months). The median tumor size at the start of chemotherapy in irradiated patients was 4.5 cm (range: 0-15 cm) versus 3 cm (range: 0-7 cm) in nonirradiated patients (p = 0.004). The irradiated and nonirradiated groups were not significantly different in terms of tumor scores. Radiotherapy improved (p = 0.001) local control (5-year rates: 89% versus 52%) for Stages III and IV combined. This benefit was due to the dramatic improvement (p = 0.0009) in local control for patients with lymphomas measuring > or =4 cm at the start of chemotherapy (5-year rates: 89% for irradiated patients versus 33% for nonirradiated patients). Radiotherapy also improved (p = 0.003) freedom from progression (5-year rates: 85% for irradiated patients versus 51% for nonirradiated patients) for Stages III and IV combined. On multivariate analysis, radiotherapy was the most significant factor affecting local control and freedom from progression. Overall survival was not significantly different (p = 0. 620) between irradiated and nonirradiated patients (5-year rates: 87% versus 81%, respectively). When Stages III and IV were analyzed separately, radiotherapy improved local control and freedom from progression but not overall survival. Radiotherapy was tolerated reasonably well, with the main toxicity being moderate myelosuppression. Eleven out of 12 (92%) patients with recurrent disease at the time of their last follow-up visit were treated initially with chemotherapy alone. CONCLUSION: Involved field radiotherapy improved local control and freedom from progression in patients with > or = 4 cm Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to CHOP-based induction chemotherapy. Involved field radiotherapy was tolerated reasonably well.     

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue arising in the extracranial head and neck region: a high rate of dissemination and disease recurrence

Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma, although generally indolent in nature, has variable and heterogeneous clinical course and biologic behavior. We have evaluated the clinical features and follow-up of patients with MALT lymphomas involving the head and neck in our institution. Forty-four new patients with MALT lymphomas arising in ocular adnexa (24 patients, group A) and other head and neck sites (20 patients, group B) of the salivary gland (13), thyroid gland (3) and other regions (4) were retrospectively analyzed. At initial diagnosis, 21 patients had solitary lesions (16/24 in the group A vs. 5/20 in the group B, P=.008); 23 had disseminated disease at multiple sites (11 patients) and/or lymph node involvement (15 patients: 3/24 in the group A vs. 12/20 in the group B, P=.025). Treatment consisted of local therapy, consisting of surgical resection and/or radiotherapy, in 34 patients and systemic chemotherapy with/without local therapy in 10 patients. Eight patients experienced tumor recurrence: four patients died of disease, two were alive with disease, and two were disease-free at last follow-up. With a mean follow-up of 46 months, the 5-year overall survival and relapse-free rates were 83% and 74%, respectively, which did not differ between the two groups (P>.5). Patients with MALT lymphomas of the head and neck are at relatively high risk for multifocal or lymph node involvement. Recurrence at prolonged times after therapy indicates the need for close long-term monitoring, and for prospective trials to prevent recurrence.     

Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

PURPOSE: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. PATIENTS AND METHODS: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO2 laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). RESULTS: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). CONCLUSION: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.     

Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy

This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.     

Factors that affect response to chemotherapy and survival of patients with advanced head and neck cancer.

A review of 164 patients with far advanced head and neck cancer, treated by a cytotoxic chemotherapy over a ten year period, at WAyne State University, Detroit, Michigan, was done in an attempt to determine factors that may influence the response to chemotherapy and subsequent survival. Response rate to methotrexate was 28%, 5-FU 31%, and porfiromycin 13%. Improved responses were noted with combination chemotherapy. Patients who failed to first line therapy rarely responded to other single agent or combination chemotherapy. Those who did not have prior surgery and/or radiotherapy had better results from drug therapy. Patients with good performance status at the time of initial chemotherapy, had better response to treatment (32% vs. 13% PR & CR) and longer survival (28 weeks vs. 9 weeks, p = 0.01) when compared to those with poor status. Patients who responded to chemotherapy have better survival compared to nonresponders (29 weeks vs. 16 weeks, p = 0.002). This information may prove helpful in future planning of multidisciplinary approach in the treatment of patients with head and neck cancer.     

Results with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiotherapy with or without prechemotherapy surgical debulking for patients with bulky, aggressive lymphoma

BACKGROUND: The authors performed a case-control analysis of local control, progression free survival, and overall survival in patients with Stage I-II aggressive lymphomas measuring > or = 7 cm in greatest dimension who were treated initially with or without surgical debulking: All patients then received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) based chemotherapy followed by involved field radiotherapy. METHODS: From May 1975 through May 1996, 50 patients were treated with (n = 25 patients) or without (n = 25 patients) resection of > 80% of their bulky lymphomas. Chemotherapy consisted of 3-12 cycles of CHOP. In general, patients who underwent debulking received three cycles of chemotherapy, whereas patients who did not undergo debulking received at least six cycles of chemotherapy. The total radiotherapy dose was 40.8 grays (Gy) +/- 4.2 Gy (mean +/- standard deviation). RESULTS: The median follow-up was 62 months. Patients who underwent debulking were similar prognostically to patients who did not. There was a trend toward improved local control (5 year rates: 96% vs. 80%; P = 0.10) and overall survival (5 year rates: 83% vs. 71%; P = 0.18) in patients who underwent debulking compared with patients who did not, respectively. Progression free survival was significantly better for patients who underwent debulking compared with patients who did not (5 year rates: 88% vs. 62%, respectively; P = 0.04). CONCLUSIONS: Because this study was retrospective, selection bias may account for the observed difference in progression free survival. Because it is unlikely that a trial randomizing patients with bulky, aggressive lymphoma to surgery will be conducted, the authors' current efforts are focused on escalation of the total radiotherapy dose as a possibly less costly and less morbid approach toward improving progression free survival for these patients.     

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.     

Treatment outcomes and prognostic features in adenoid cystic carcinoma originated from the head and neck

Surgery is the main treatment modality for adenoid cystic carcinoma (ACC) originated from the head and neck. However, the extensive local infiltrative and perineural spread related to this malignancy often cause difficulty to achieve high tumor control. The aim of this study is to evaluate the efficacy of postoperative radiotherapy (RT) in ACC, and to identify prognostic variables associated with treatment outcomes. A retrospective review of 101 patients diagnosed with ACC in the head and neck region was performed. T stage distribution was T1, 25; T2, 35; T3, 18; and T4, 23 patients. All patients were grouped into two arms: surgery alone or combined with postoperative radiotherapy. The 5-year local-regional control (LRC), overall survival (OS) and disease-free survival (DFS) rates for all the patients were 70.5%, 91.7% and 63.2%, respectively. On univariant analysis, postoperative radiotherapy did improve the 5-year LRC and DFS compared to surgery alone (81.0% vs. 53.4%, p=0.0003 and 71.3% vs. 50.0%, p=0.0052, respectively). And patients with T1-T2 lesions achieved better treatment outcomes, whereas stage T3-T4 was associated with high local failure and poor disease-free survival. Furthermore, multivariate analysis revealed that the addition of radiotherapy and early lesions were both favorite predictors for local control and survival rates. The prognosis for ACC of the head and neck was excellent. Surgery combined with postoperative radiotherapy significantly reduced the local failure, and further improved disease-free survival. Nevertheless, the relatively high distant metastasis was an obstacle of curing the ACC patients.     

Locally advanced stage IV squamous cell carcinoma of the head and neck: impact of pre-radiotherapy hemoglobin level and interruptions during radiotherapy

PURPOSE: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. METHODS AND MATERIALS: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy>1 week. RESULTS: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p=.012), hemoglobin>or=12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p=.048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p=.021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p=.013), hemoglobin>or=12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p<.001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p=.008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p=.015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p=.012). CONCLUSIONS: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy>1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.     

Prognostic factors of stage I and II non-Hodgkin's lymphomas of the head and neck: the value of the working formulation and need for chemotherapy

From 1966 through 1984, 142 patients with early stage non-Hodgkin's lymphoma of the head and neck were treated. Histologic slides were reviewed and reclassified according to Rappaport's classification and the Working Formulation. Patients were clinically staged; 82 Stage I, and 60 Stage II. Five-year freedom from relapse was 53% for Stage I and 48% for Stage II patients with no statistically significant difference. No patients with favorable histologies of Rappaport's classification or low grade malignancy of the Working Formulation relapsed. By univariate analyses, stage, primary site, the Working Formulation, Rappaport's classification, extent of radiation field, radiation dose, tumor bulkiness and addition of multiple-agent chemotherapy seemed to be prognostic factors for predicting relapse. Multivariate regression analyses (MVA) showed primary site and multiple-agent chemotherapy were independent prognostic factors. Tumor bulkiness provided marginal prognostic significance. Waldeyer's ring lymphomas fared better than nodal or extralymphatic lymphomas; it seems necessary to report Waldeyer's ring lymphomas independently from nodal or extralymphatic lymphomas. Patients receiving more than 3 chemotherapeutic agents had better prognosis than those receiving 3 or less agents, or no chemotherapy. Pathologic grade was another prognostic factor when the Working Formulation was used in MVA. When Rappaport's classification was used, division of unfavorable histologies into histiocytic and non-histiocytic groups provided only marginal significance in MVA. We conclude that Stage I-II non-Hodgkin's lymphomas of the head and neck with favorable histologies of Rappaport's classification or low grade malignancy of the Working Formulation be treated with radiation therapy only; and patients with other histologies should be treated with multiple-agent chemotherapy and radiation therapy.     

Multidrug chemotherapy using bleomycin, methotrexate, and cisplatin combined with radical radiotherapy in advanced head and neck cancer

Thirty-one patients with Stage III-IV head and neck squamous cell cancer were treated by three courses of combination chemotherapy using bleomycin, methotrexate, and cisplatin followed by a radical course of radiation and in two cases by surgery. Of 29 evaluable patients, 4 (14%) achieved complete remission (CR) with chemotherapy and 13 (45%) had a partial response (PR). With the addition of radiotherapy and surgery, the CR rate increased to 72%. At 30 months the actuarial survival of all evaluable patients was 61% and of complete responders, 76%. Patients with nasopharyngeal cancer had an actuarial survival of 80% at 30 months, whereas patients with squamous malignancies at other sites in the head and neck region had an actuarial survival of only 37%. Side effects were tolerable. It is concluded that complete responders to combination chemotherapy and radiotherapy have a survival benefit at 30 months. The combined approach is most effective in nasopharyngeal cancer.     

Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy

PURPOSE: To examine the efficacy of fast neutron radiotherapy for the treatment of locally advanced and/or recurrent adenoid cystic carcinoma of the head and neck and to identify prognostic variables associated with local-regional control and survival. METHODS AND MATERIALS: One hundred fifty-nine patients with nonmetastatic, previously unirradiated, locally advanced, and/or recurrent adenoid cystic carcinoma (ACC) of the head and neck region were treated with fast neutron radiotherapy during the years 1985-1997. One hundred fifty-one patients had either unresectable disease, or gross residual disease (GRD) after an attempted surgical extirpation. Eight patients had microscopic residual disease and were analyzed separately. Sixty-two percent of patients had tumors arising in minor salivary glands, 29% in major salivary glands, and 9% in other sites such as the lacrimal glands, tracheal-bronchial tree, etc. Fifty-five percent of patients were treated for postsurgical recurrent disease and 13% of patients had lymph node involvement at the time of treatment. The median duration of follow-up was 32 months (range 3-142 months). Actuarial curves for survival, cause-specific survival, local-regional control, and the development of distant metastases are presented for times out to 11 years. RESULTS: The 5-year actuarial local-regional tumor control rate for the 151 patients with GRD was 57%; the 5-year actuarial overall survival rate was 72%; and the 5-year actuarial cause-specific survival rate was 77%. Variables associated with decreased local-regional control in the patients with GRD as determined by multivariate analysis included base of skull involvement (p < 0.01) and biopsy only versus an attempted surgical resection prior to treatment (p = 0.03). Patients without these negative factors had an actuarial local-regional control rate of 80% at 5 years. Patients with microscopic residual disease (n = 8) had a 5-year actuarial local-regional control rate of 100%. Base of skull involvement (p < 0.001), lymph node metastases at the time of treatment (p < 0.01), biopsy only prior to neutron radiotherapy (p = 0.03), and recurrent tumors (p = 0.04) were found to be associated with a diminished cause-specific survival as ascertained by multivariate analysis. Patients with base of skull involvement and positive lymph nodes at presentation had an increased rate of the development of distant metastases at 5 years, (p < 0.01 and p < 0.001, respectively). No statistical difference in outcome was observed between major and minor salivary gland sites. CONCLUSIONS: Fast neutron radiotherapy is an effective treatment for locally advanced ACC of the head and neck region with acceptable toxicity. Further improvements in local-regional control are not likely to impact survival until more effective systemic agents are developed to prevent and/or treat distant metastatic disease.     

Extranodal lymphoma of the head and neck area

Records of 64 patients with extranodal lymphoma of the head and neck area treated at this institution between 1965 and 1982 have been reviewed. Of these cases, 78% had Stage I-EA disease, 20% had Stage II-EA disease, and 2% had Stage III-EA disease. Excluded from this study were patients of the pediatric age, patients with previous chemotherapy and surgery, patients in whom extranodal involvement has been a terminal manifestation of wide-spread disease, and patients with nodal involvement with extension of disease outside the lymph nodes. Patients with a histiocytic histology accounted for 63%, 28% were of lymphocytic histologies, 4.5% were of mixed histologies, and in 4.5% a diagnosis of lymphoma or benign lymphocytic proliferation had been made. The paranasal sinuses, nasal cavity, and oral cavity were the most frequent sites of involvement, making up 39% of the cases--with the orbit, central nervous system, nasopharynx, salivary glands, thyroid, skin, and larynx following in that order of frequency. All patients received a definitive course of radiotherapy, except patients with CNS involvement. In no case was chemotherapy given concomitantly with the radiation therapy. One-third of the patients did require chemotherapy at a later time for progression of disease. No patients were lost to follow-up. Seven patients with primaries of the brain were inevaluable for response; however, all patients having visible or palpable tumors achieved a complete response (100%), and there was no recurrence or persistent disease in the field of therapy. The next area of disease involvement depended on the site of the primary. Nodal involvement following extranodal disease carried a poor prognosis.     

Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer

PURPOSE: Neck dissection has traditionally played an important role in the treatment of patients with squamous cell carcinoma of the head and neck who present with regionally advanced neck disease (N2-N3). Radiotherapy and concurrent chemotherapy improves overall survival in advanced head-and-neck cancer compared with radiotherapy alone. The necessity for postchemoradiation neck dissection is controversial. The intent of this report was to define the value of neck dissection in this patient population better. METHODS AND MATERIALS: Patients with locally advanced squamous carcinoma of the head and neck who also presented with nodal disease and underwent hyperfractionated radiotherapy and concurrent cisplatin/5-fluorouracil chemotherapy constituted the study population. Adjuvant modified neck dissection (MND) was planned 6 to 8 weeks after completion of chemoradiation in those patients who had a biopsy-proven pathologically complete response at the primary tumor site, irrespective of the clinical/radiographic neck response. A cohort of patients underwent electrode assessment of tumor oxygenation. Pathologic findings from the MND were used to compute the negative and positive predictive values and overall accuracy of the clinical/radiographic response (cCR). Regional control, failure-free survival, and survival were compared according to whether patients actually underwent MND. RESULTS: A total of 154 patients received concurrent chemoradiation. Of these, 108 presented with nodal disease: N1, n = 30; and N2-N3, n = 78. MND was performed in 65 (60%) of 108 patients, including 13 (43%) of 30 with Stage N1 and 52 (66%) of 78 with Stage N2-N3. For N1 patients, the negative predictive value of a cCR, positive predictive value of less than a cCR, and the overall accuracy for clinical response was 92%, 100%, and 92%, respectively. For N2-N3 patients, the corresponding values were 74%, 44%, and 60%. Patients with poorly oxygenated tumors were more likely to have residual disease at MND. The median follow-up was 4 years. The 4-year disease-free survival rate was 70% for N1 patients, irrespective of the clinical response or whether MND was performed. The 4-year disease-free survival rate was 75% for N2-N3 patients who had a cCR and underwent MND vs. 53% for patients who had a cCR but did not undergo MND (p = 0.08). The 4-year overall survival rate was 77% vs. 50% for these two groups of patients (p = 0.04). CONCLUSION: The clinical and pathologic responses in the neck correlated poorly with one another for patients with N2-N3 neck disease undergoing concurrent chemoradiation for advanced head-and-neck cancer. MND still appears to confer a disease-free survival and overall survival advantage with acceptably low morbidity. Tumor oxygenation assessment may be useful in selecting patients who are especially prone to have residual disease. Better tools need to be developed to determine prospectively whether this procedure is required for individual patients.     

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non-small-cell lung cancer treated with induction chemotherapy followed by surgery

PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.     

Primary thyroid lymphoma: the 40 year experience of a UK lymphoma treatment centre

We report the 40-year unselected experience of a UK lymphoma treatment centre. Between 1970 and 2010, 3363 cases of non-Hodgkin lymphoma were managed by the Sheffield Lymphoma Team. Seventy cases of primary thyroid lymphoma were identified during this time. This retrospective review of the clinical and pathological features of patients with thyroid lymphoma comprises one of the largest series conducted in the UK. The series included 57 females and 13 males with a median age at diagnosis of 69.5. The pathological subtypes were diffuse large B-cell lymphoma (DLBCL) in 50 patients, MALT lymphoma in 13, indolent B-cell lymphoma not otherwise specified (NOS) in 6 and T cell lymphoma in one patient. Of the 64 patients fully staged, 53 had Stage IE and 11 Stage IIE disease. Management modalities included surgery, chemotherapy, radiotherapy or combination treatment. Five- year survival rates for DLBCL, MALT lymphoma and indolent B-cell lymphoma NOS were 45%, 62% and 75%, respectively, with a median overall survival of all histological subtypes of 68 months (range 0-148) or 5.7 years. The outcomes of this series confirm previous experience. If treatment is needed after surgery radiotherapy alone is sufficient for Stage I and II low grade thyroid lymphoma. Combination chemotherapy or adequate chemotherapy followed by radiotherapy is warranted in high grade thyroid lymphoma.     

Extranodal non-Hodgkin's lymphoma of the head and neck. A clinicopathologic study in the Kyoto-Nara area of Japan

The clinicopathologic features of 114 Japanese patients with extranodal non-Hodgkin's lymphoma of the head and neck region were analyzed. The median age was 60.5 years and the male:female ratio was 1.5:1. The most common site of involvement was Waldeyer's ring, followed by the oral cavity, thyroid gland, paranasal sinuses, nasal cavity, and larynx. Seventy-five percent of the patients were in Stage I or Stage II at admission. Histologically, diffuse lymphoma accounted for 94% and follicular lymphoma for 6% of cases. The histologic grade according to the Working Formulation System of the National Cancer Institute was low in 11%, intermediate in 75%, and high in 14% of cases. Immunohistochemical study showed that the majority of the cases were of B-cell type and only 13 cases (11%) were of the T-cell type. Peripheral T-cell lymphomas (eight cases) mainly occurred in the nasopharynx and nasal cavity, whereas four of five thymic T-cell lymphomas were found in the palatine tonsil. The over-all 5-year survival rate was 54%, and the factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage, and the site of initial presentation. Five-year survival with nasal cavity and Waldeyer's ring lymphoma was 24% and 46%, respectively. The poor prognosis of lymphomas at these sites might result from the predominance of T-cell lymphoma, the paucity of low grade lymphoma, and the relatively high incidence of cases that were in an advanced stage at presentation. In Stage II, patients treated with combined therapy tended to have a better 5-year survival rate than those treated with radiotherapy alone.     

Toxic cure: Hyperfractionated radiotherapy with concurrent cisplatin and fluorouracil for Stage III and IVA head-and-neck cancer in the community

PURPOSE: To evaluate efficacy and toxicity of the Duke University chemoirradiation regimen for locally advanced head-and-neck cancer in a regional community cancer center. METHODS AND MATERIALS: Between June 1998 and June 2002, 50 patients with Stage III or IVA squamous cell carcinoma of the head and neck were treated definitively with concurrent combined modality therapy (CMT). Patients received accelerated, hyperfractionated radiotherapy (AFRT), 1.2-1.25 Gy b.i.d., to a median prescribed dose of 70 Gy. Chemotherapy consisted of cisplatin 12 mg and fluorouracil 600 mg/m(2) daily for 5 consecutive days during Weeks 1 and 6, followed by two cycles after AFRT. Patients with N2-N3 neck disease (n = 21; 42%) were considered for neck dissection depending on their response to AFRT and chemotherapy. Twenty-nine patients with Stage III and IVA disease treated between 1991 and 1997 with definitive RT alone served as historical controls. RESULTS: Forty-nine patients (98%) in the CMT group completed the prescribed AFRT and 38 (76%) completed four cycles of chemotherapy. Three of 8 patients who underwent neck dissection had a pathologically complete response. The median follow-up for all patients was 23 months. The actuarial progression-free survival rate at 2 years was 75% for the CMT group vs. 40% (p <0.01) for the RT group. The overall survival rate was 80% and 43% (p <0.01), respectively, for the CMT and RT groups. Acute Radiation Therapy Oncology Group Grade 3 toxicities for the CMT group were mucosal (n = 50; 100%), skin (n = 9; 18%), and hematologic (n = 3; 6%). Late Grade 3-4 toxicities consisted of pharyngeal stricture (n = 7; 14%), laryngeal chondritis (n = 3; 6%), osteoradionecrosis (n = 2; 4%), and peripheral neuropathy (n = 1; 2%). CONCLUSION: This aggressive regimen of AFRT with concurrent cisplatin and fluorouracil with or without neck dissection is feasible in the community setting for patients with Stage III and IVA head-and-neck cancer. Early results indicated excellent survival, albeit with universal acute mucosal, and considerable, although acceptable, late toxicity.     

Recurrent head-and-neck chemodectomas: a comparison of surgical and radiotherapeutic results

PURPOSE: To compare the outcome of salvage radiotherapy (RT) and surgery for recurrent head-and-neck chemodectomas. MATERIALS AND METHODS: We retrospectively studied 70 patients with benign chemodectomas of the head and neck treated with surgery at the Cleveland Clinic between July 1969 and August 1999; 29 of these patients were diagnosed with recurrent tumors. Salvage RT was used in 12 patients (gamma knife radiosurgery for 7, conventional external beam RT for 4, and intensity-modulated RT for 1 patient). The median follow-up was 55 months for the entire group of 70 patients. RESULTS: The median time to recurrence was 36 months. Of the recurrences, 16 were glomus jugulare, 7 were carotid body tumors, 5 were glomus tympanicum, and 1 was thyroid paraganglioma. RT was used in 12 patients (9 patients with glomus jugulare, 2 with glomus tympanicum, and 1 with thyroid paraganglioma). Surgery was performed in 17 patients (7 patients with glomus jugulare, 7 with carotid body, and 3 with glomus tympanicum). For patients with glomus jugulare and glomus tympanicum tumors, the 5-year freedom from disease progression was 100% for patients treated with RT vs. 62% for those treated with surgery (p = 0.0124). Seven patients with carotid body tumors and 1 patient with thyroid paraganglioma were treated successfully with surgery and RT, respectively. No significant side effects were associated with RT; however, postoperative complications occurred in 8 of the 17 surgery patients (new cranial nerve palsies, meningitis, infection, and cerebrospinal fluid leak). CONCLUSION: Salvage RT appears superior to surgery and should be considered the treatment of choice for patients with recurrent glomus jugulare and glomus tympanicum tumors. For recurrent carotid body tumors, surgery produced excellent local control, most likely because of the easier resectability in this location.     

Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement

BACKGROUND AND PURPOSE: Post-operative radiotherapy is indicated for the treatment of head and neck cancers. In vitro, chemotherapy potentiates the cytotoxic effects of radiation. We report the results of a randomized trial testing post-operative radiotherapy alone versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. MATERIALS AND METHODS: The study involved patients undergoing curative-intent surgery for head and neck cancers with histological evidence of lymph node involvement. Patients were randomly assigned to receive radiotherapy alone (54-72Gy, 30-40 fractions, 6-8 weeks) or identical treatment plus concomitant Carboplatin (50mg/m(2) administered by IV infusion twice weekly). RESULTS: Between February 1994 and June 2002, 144 patients were included. With a median follow-up of 106 months (95% confidence interval (CI) [92-119]), the 2-year rate of loco-regional control was 73% (95% CI: 0.61-0.84) in the combined treatment group and 68% (95% CI: 0.57-0.80) in the radiotherapy group (p=0.26). Overall survival did not differ significantly between groups (hazard ratio for death, 1.05; 95% CI: 0.69-1.60; p=0.81). CONCLUSIONS: Twice-weekly administration of carboplatin concomitant to post-operative radiotherapy did not improve local control or overall survival rates in this population of patients with node-positive head and neck cancers.