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K K Ang

Publications and source records attributed to K K Ang.

At least 55 records · Page 3Linked to original sources
PubMed1998

Altered fractionation trials in head and neck cancer.

Advancement in radiobiological concepts has led to the development of two classes of new fractionation schedules for the treatment of head and neck cancers. These altered fractionation regimens are referred to as hyperfractionation and accelerated fractionation schedules. Hyperfractionation exploits the difference in fractionation sensitivity between tumors and normal tissues manifesting late morbidity. In contrast, accelerated fractionations attempt to reduce tumor proliferation as a major cause of radiotherapy failure. Although there are many permutations in accelerating radiation treatment, the existing schedules can be conceptually grouped into two categories, pure accelerated fractionations and hybrid accelerated regimens, depending on whether there are concurrent changes in other fractionation parameters. The results of 10 completed phase III clinical trials addressing different types of altered fractionation schedules in head and neck carcinomas are examined and summarized in this review article. The data of trials on hyperfractionation regimens applying 10% to 15% total dose increment over the standard 66 to 70 Gy consistently revealed a 10% to 15% improvement in the local control rate of a subset of intermediate-stage carcinomas without an appreciable increase in the incidence of late complications. The available data on accelerated fractionation regimens showed that tumor clonogen proliferation is a major cause of radiation failure. Completed studies, however, revealed that a 1- to 1.5-week treatment acceleration without total dose reduction achieved by administering 2-Gy fractions 6 times per week or concomitant boost schedule yielded an approximately 15% higher tumor control rate without increasing late toxicity. Shortening the overall time to less than 2 weeks with an associated total dose reduction did not seem to improve tumor control rate, with an exception perhaps for a small subset of patients with laryngeal carcinomas, but might decrease some late normal tissue injury. A weekly dose accumulation rate of 14 Gy or greater, or delivery of 3 fractions of 1.6 Gy/d, with 6 hour intervals, without total dose reduction, was found to increase morbidity beyond the acceptable level. Further treatment refinements building on these findings are being pursued.

Dose Fractionation, Radiation↗
PubMed1998

Altered fractionation in the management of head and neck cancer.

Progress in radiation science led to the development of two classes of biologically sound fractionation schedules for the treatment of head and neck cancers. These altered fractionation regimens are referred to as hyperfractionation and accelerated fractionation schedules. Hyperfractionation exploits the difference in fractionation sensitivity between tumours and tissues manifesting late morbidity and only minor variations exist among regimens tested. In contrast, accelerated fractionation attempts to reduce tumour proliferation as a major cause of radiotherapy failure. Although there are major permutations, the existing schedules can conceptually be grouped into two categories, namely pure accelerated fractionation and hybrid accelerated regimens, depending on whether there are concurrent changes in other fractionation parameters. The results of completed phase III clinical trials addressing different types of altered fractionation schedules in head and neck carcinomas are summarized and examined in this review paper. The data from trials on hyperfractionation regimens applying 10-15% total dose increment consistently revealed a 10-15% improvement in the local control rate of a subset of intermediate-stage carcinomas without increasing the incidence of late complications. The available data on accelerated fractionation regimens already showed that tumour clonogen proliferation is a major cause of radiation failure. However, completed studies revealed that a 1-1.5 week treatment acceleration without total-dose reduction, achieved by administering 2 Gy fractions six times per week or concomitant boost schedule, yielded a 15% higher tumour control rate without increasing late toxicity. Shortening the overall time to below 2 weeks with an associated total-dose reduction did not seem to improve the tumour control rate but might decrease some late normal-tissue injury. A weekly dose accumulation rate of > or =14 Gy or delivery of three fractions of 1.6 Gy per day, with a 6 h interval, without total-dose reduction was found to increase morbidity significantly. Further treatment refinements are being pursued based on these findings.

Clinical Trials, Phase III as Topic↗
PubMed1998

The effects of preoperative irradiation on peripheral nerve regeneration.

The purpose of this study was to evaluate the effects of preoperative external cobalt60 beam irradiation on nerve regeneration. Ninety 250-g male Sprague-Dawley rats were studied. Peripheral nerve regeneration was measured by walking track analysis and histomorphology of the proximal, grafted, and distal nerve segments. Ninety animals were randomly assigned to one of five treatment groups, receiving a total fractionated dose of 30, 50, 70, and 90 Gy. Each animal received a 15-mm interposition nerve graft into the right posterior tibial nerve 6 weeks following completion of radiation therapy. The left leg served as a control. The remaining 10 animals received a nerve isograft subjected to a single dose of 30 Gy prior to placement (group 5). Walking track analysis was performed monthly through 8 months. At the conclusion of 120 and 240 days, sections of the proximal, grafted, and distal nerve were harvested, stained, and examined histomorphologically. Evaluation of the print length index demonstrated no statistical difference between our previously established nonirradiated controls, the irradiated groups, and the irradiated isograft group (group 5). The total number of axons per square millimeter was significantly decreased in the distal segment of all irradiated groups when compared with the controls. No statistical difference in number of axons per square millimeter was noted in the irradiated isograft group. Furthermore, no statistical difference was noted in the nerve fiber density between the control group, the preoperative irradiated groups, or the irradiated isograft group (group 5). Despite the reduction in myelinated regenerating fibers, no reduction in function was observed as measured by walking track analysis. Thus, immediate reconstruction of peripheral nerve defects in the face of preoperative irradiation may not be contraindicated.

Animals↗
PubMed1998

Radiation therapy for early stage (T1-T2) sarcomatoid carcinoma of true vocal cords: outcomes and patterns of failure.

Sarcomatoid carcinoma of head and neck mucosal sites is a rare high-grade malignancy that may cause diagnostic and therapeutic controversies. A characteristic of this entity consistently reported but not entirely validated is its relative radioresistance and the general belief is that surgery is the treatment of choice. The objective of this retrospective study was to determine if patients treated with radiation for early glottic sarcomatoid carcinoma had worse outcomes than those achieved with irradiation for the more typical squamous cell carcinoma. Twenty-eight cases of early stage (T1-T2) sarcomatoid carcinoma of the larynx treated with definitive doses of megavoltage irradiation between 1969 and 1995 at The University of Texas M. D. Anderson Cancer Center form the cohort for this analysis. All pathologic material was reviewed to confirm the diagnosis. All tumors manifested spindle cell features with marked cytomorphologic abnormalities characteristic of this entity. Sixteen tumors (57%) had the more typical polypoid gross morphology of sarcomatoid carcinoma. Twenty-one patients (75%) were staged T1 and seven patients (25%) had stage T2 disease. All patients were treated with small laryngeal fields, median size 20 cm2, and to a median dose of 65 Gy. Follow-up ranged from 1.5 to 24 years (median, 10 years). Four patients (14%) had local disease recurrence, and all had salvage total laryngectomies and remained free of local disease. The 5-year actuarial local control rates for patients with T1 and T2 lesions were 94% and 54%, respectively. Only one patient developed regional and distant disease. The 10-year actuarial disease-specific and overall survival rates were 92% and 63%, respectively. Patients with early stage sarcomatoid carcinoma of the glottis treated with radiation had similar control rates to irradiated patients with similar volume disease with the more typical squamous cell carcinoma. The authors contend that the histologic diagnosis of sarcomatoid carcinoma by itself should not influence the decision to treat a patient with early stage glottic disease with irradiation.

Adult↗
PubMed1998

Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma.

PURPOSE: To assess the activity and toxicity profile of combined taxol (paclitaxel), ifosfamide, and platinum (cisplatin) (TIP) in patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck. PATIENTS AND METHODS: Recurrent or metastatic head and neck SCC patients received paclitaxel 175 mg/m2 in a 3-hour infusion on day 1; ifosfamide 1,000 mg/m2 in a 2-hour infusion on days 1 through 3; mesna 600 mg/m2 on days 1 through 3; and cisplatin 60 mg/m2 on day 1, repeated every 3 to 4 weeks. All were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic hematopoietic growth factors were not permitted. RESULTS: Fifty-two patients were assessable for response and toxicity; 53 for survival (local-regional recurrence alone in 57% and distant metastasis with or without local-regional recurrence in 43%). Overall response rate was 58% (30 of 52) of patients; complete response rate was 17% (nine of 52) of patients, with six complete responses that continued for a median 15.7+ months. Median follow-up of all patients was 17.7 months. Median survival was 8.8 months (95% confidence interval [CI] 8.1 to 17.5 months). Toxicity was relatively well tolerated and caused no deaths. The most frequent moderate-to-severe toxicity (90% of patients) was transient grades 3 to 4 neutropenia; neutropenic fever occurred in 27%. Grade 3 peripheral neuropathy occurred in three patients, none had grade 4. Grade 3 mucositis occurred in only one patient, none had grade 4. CONCLUSION: TIP had major activity in this setting, with a 58% objective response rate, 17% complete response rate, durable complete responses (six of nine persisting), and relatively well-tolerated toxicity, with no toxic deaths. The activity of TIP, a novel taxol-cisplatin-based regimen, in recurrent or metastatic head and neck SCC should be confirmed in a phase III trial.

Adult↗
PubMed1997

Concomitant boost radiotherapy for squamous carcinoma of the tonsillar fossa.

PURPOSE: To assess the efficacy of a concomitant boost fractionation schedule of radiotherapy for treating patients with squamous carcinoma of the tonsillar fossa. PATIENTS AND METHODS: Between December 1983 and November 1992, 83 patients with squamous carcinoma of the tonsil were treated with concomitant boost fractionation. The distribution of American Joint Committee on Cancer T stages was TX-4, T1-5, T2-29, T3-41, T4-4; N stages were NX-1, N0-26, N1-13, N2-31, N3-12. Patients were treated with standard large fields to 54 Gy in 6 weeks. The boost treatment consisted of a second daily 1.5 Gy fraction for 10-12 fractions, usually delivered during the final phase of treatment. The tumor dose was 69-72 Gy, given over 6 weeks. Twenty-one patients, who all had N2 or N3 regional disease, underwent neck dissections, either before (13 patients) or 6 weeks after radiotherapy (8 patients); the other patients were treated with radiotherapy alone. RESULTS: The 5-year actuarial disease-specific survival and overall survival rates were 71 and 60%, respectively. Patients with T2 and T3 primary tumors had 5-year actuarial local control rates of 96 and 78%, respectively. Patients with T3 disease who received the final-phase boost had a 5-year actuarial local control rate of 82%. Actuarial 5-year regional disease control rates were N0, 92%; N1, 76%; N2, 89%; and N3, 89%. The 21 patients who had neck dissections all had their disease regionally controlled. Patients presenting with nodal disease or after a node excision who were treated with radiation alone had a 5-year actuarial regional disease control rate of 79%. All but five patients had confluent Grade 4 mucositis during treatment. Severe late complications attributable to radiation included mandibular necrosis [1], in-field osteosarcoma [1], and chronic dysphagia for solid foods [5]. CONCLUSIONS: High rates of local and regional disease control were achieved with the concomitant boost fractionation schedule, with few cases of severe late morbidity. Patients with N2 and N3 neck disease were effectively treated with radiation and the selective use of neck dissections. The concomitant boost schedule is our preferred fractionation approach for treating patients with intermediate stage tonsil cancer who are not participating in our current research protocols.

Adult↗
PubMed1997

Induction chemotherapy followed by radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma: results of a matched cohort study.

BACKGROUND: Prospective randomized and retrospective studies on adjunctive chemotherapy in patients with advanced locoregional nasopharyngeal carcinoma have yielded conflicting results and the role of chemotherapy in this disease had not been clearly defined. The authors report the results of a single institution, matched cohort study comparing a group of 61 patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy followed by radiation therapy with a matched group treated with radiotherapy alone. METHODS: Between 1985 and 1992, 61 patients with advanced locoregional nasopharyngeal carcinoma received induction chemotherapy (cisplatin, 100 mg/m2 on Day 1 and 5-fluorouracil [5-FU], 1000 mg/m2, on Days 1-5) for 3 cycles followed by definitive radiation therapy (CT/RT group). This group was matched with a group of 61 patients from a population of 378 patients who received radiation therapy alone (RT group). Matching characteristics were T classification, N classification, histology, and level of cervical lymph node metastases. These characteristics were found to be significant determinants of distant metastasis (DM) and/or survival in a multivariate analysis that was performed in the entire radiotherapy group. Radiation therapy consisted of 66-72 gray in 6.5 to 7 weeks in both groups. Fifty-nine patients (97%) in both groups had Stage IV disease. Fifteen patients (25%) in both groups had lower cervical lymph node metastases. The tumor histologic types also had similar distribution in both groups. Median follow-up time among surviving patients of the CT/RT group was 4.9 years (range, 1.3-9.8 years). RESULTS: The 5-year cumulative incidence of DM was 19 +/- 5% for the CT/RT group and 34 +/- 6% for the RT alone group (P = 0.019; log rank test). This reduction in distant failure was more prominent in patients with intermediate (N2-N3 disease; upper or midcervical lymph nodes), or high risk (N2-N3 disease; lower cervical lymph nodes) of DM. This reduction in DM translated into improvement in disease free survival (DFS) and overall survival (OS). The 5-year actuarial DFS rates were 64 +/- 6% for the CT/RT group compared with 42 +/- 7% for the RT group (P = 0.015). The 5-year actuarial OS rates were 69 +/- 6% (CT/RT group) and 48 +/- 7% (RT group), respectively (P = 0.012). The incidence of locoregional failure was slightly lower in the CT/RT group, but this difference did not reach statistical significance. There was no significant difference in the incidence and severity of acute mucositis between the two groups during radiotherapy. The 5-year cumulative incidence of Grade 3 or higher late complications was also similar in both groups (5 +/- 3% in the CT/RT group and 8 +/- 3% in the RT group; P = 0.721). CONCLUSIONS: This matched cohort study provides additional evidence that induction cisplatin-5-FU chemotherapy prior to definitive radiation improves freedom from distant metastasis, DFS, and OS for patients with locoregional Stage IV nasopharyngeal carcinoma without increasing treatment-related morbidity.

Adolescent↗
PubMed1997

Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local and regional control.

PURPOSE: This retrospective study was conducted to review the results of treatment and to identify prognostic factors for local and regional control in a population of 378 patients with nasopharyngeal carcinomas treated in a single institution by radiation therapy alone. METHODS AND MATERIAL: All patients were treated at The University of Texas M. D. Anderson Cancer Center between 1954 and 1992 following a consistent treatment philosophy but with evolving technique. There were 286 males and 92 females with a median age of 52 years (range: 16-86 years). The majority of the patients were Caucasian (282 patients, 75%). Thirty-two patients (8%) had one or more cranial nerve deficits. Three-fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3 164 patients). Histologically, 193 tumors (51%) were squamous cell carcinomas, 154 (41%) lymphoepitheliomas, and 31 (8%) unclassified carcinomas. Average total dose varied with T-stage and ranged from 60.2 to 72.0 Gy. Median follow-up time was 10 years. RESULTS: For the entire population the 5-, 10-, and 20-year actuarial survival rates were 48, 34, and 18%, respectively, with 184 patients (49%) dying of nasopharyngeal cancer. Actuarial control rates at 5, 10, and 20 years were 71, 66, and 66% for the primary site and 84, 83, and 83% for the neck. A total of 100 patients (26%) had local failures and 51 patients (13%) had regional failures with a median time to recurrence of 8.2 months and 13 months, respectively. Advanced T-stage, squamous histology, and presence of cranial nerve deficits were poor prognostic factors for local control in both univariate and multivariate analyses. N-stage and tumor histology were significant factors for neck control. Treatment year, total dose within the ranges used, and duration of treatment did not have any significant effect on local or regional control. The actuarial incidence of Grade 3-5 late complications was 16, 19, and 29% at 5, 10, and 20 years, respectively. Twelve patients (3%) died of treatment-related complications; all but one fatal complication occurred before 1971 and the other in 1976. CONCLUSIONS: This study shows very good long-term local and regional control rates for nasopharyngeal carcinomas after definitive radiotherapy and establishes a benchmark for newer treatment strategies. Improvements in treatment technique over the years have dramatically reduced the frequency of severe late complications. Patients with advanced stage tumors and differentiated squamous histology have a relatively poor prognosis when treated with conventional radiotherapy and are candidates for dose escalation or combined modality studies.

Adolescent↗
PubMed1997

Postoperative radiotherapy for malignant tumors of the parotid gland.

PURPOSE: To update our experience using postoperative irradiation in selected patients with carcinomas of the parotid gland. Outcomes of treatment with a focus on the effectiveness of the two primary techniques of radiation used for treating these tumors were evaluated. METHODS AND MATERIALS: A retrospective analysis of 166 patients with parotid gland malignancies treated in the Department of Radiotherapy at the University of Texas M. D. Anderson Cancer Center between 1965-1989 was performed. All patients were treated following surgery and did not have macroscopic disease at the time of their radiation. The most common histologies were mucoepidermoid carcinoma (28%) and adenocarcinoma (27%). Pathologic features constituting indications for postoperative radiotherapy included: inadequate margins, 104 (63%) cases; extraglandular disease extension, 82 (49%); perineural invasion 57 (34%); and nodal disease 43 (26%). Radiation was delivered through an ipsilateral field of predominantly high energy electrons in 142 patients (86%). Wedged paired 60Co fields were used to treat 19 patients. The median dose was 60 Gy, typically delivered at 2 Gy per fraction. The median follow-up time for surviving patients was 155 months. RESULTS: Forty-seven (29%) patients had disease recurrence, of whom 15 (9%) had disease recur locally and 10 (6%) regionally (neck). There was no association between the dose of radiation and local failure, except for a trend for patients with positive margins and/or named nerve involvement to have improved local control if they received doses > 60 Gy. There was no difference in failure rates in patients treated with wedged pair techniques or ipsilateral fields, but there was a higher complication rate in the former. Overall, 37 patients (22%) developed chronic sequelae attributed to radiation. Twelve patients developed decreased hearing, and 15 patients developed soft tissue or bone necrosis or exposure. CONCLUSIONS: Local and regional control rates for high risk patients with parotid gland carcinomas treated with radiation following surgery were excellent. The technique of using an ipsilateral field encompassing the parotid bed and treated with high energy electrons often mixed with photons was effective with minimal severe late toxicity. The moderate complication rate experienced in this series can be further reduced using modern techniques as described.

Adenocarcinoma↗
PubMed1997

Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival.

PURPOSE: This retrospective study was conducted to identify the prognostic factors for distant metastasis and survival in a population of 378 patients with nasopharyngeal carcinomas treated by radiation therapy alone. MATERIALS AND METHODS: All patients were treated at the University of Texas M.D. Anderson Cancer Center between 1954 and 1992, following a consistent dose and volume prescription policy. There were 286 males and 92 females. The median age was 52 years (range: 16-86 years). The majority of the patients were white Caucasians (282 patients,75%). Tumors were classified as squamous cell carcinomas (193; 51%), lymphoepitheliomas (154; 41%), or unclassified carcinomas (31, 8%). Three fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3 164 patients). The treatment techniques included opposed lateral fields with or without an anteroposterior or an anterior oblique pairs for dose supplementation to the primary site. Average total doses per T-stage ranged between 60.2 and 72.0 Gy. Median follow-up time was 10 years (range 0.3 to 28.6 years). RESULTS: A total of 103 patients (27%) developed distant metastases at a median time of 8 months (range: 1-90 months). Actuarial rates for distant metastasis were 30%, 32%, 32% at 5, 10, and 20 years, respectively. Actuarial rates for disease specific survival at the same time points were 53%, 45%, and 39% with 184 patients (49%) dying of their nasopharyngeal cancer. Advanced T-stage, N-stage, and non-lymphoepithelioma histology were independent adverse prognostic factors for disease specific survival. Advanced N-stage and low neck disease were independent adverse prognostic factors for distant metastasis with a very high rate of distant metastases for those patients who presented with both adverse factors (relative risk 7.86). On average, patients with distant metastasis lived 5 months after they were diagnosed with metastatic disease (range: 0-172 months), although four patients (4%) survived more than 5 years after diagnosis. CONCLUSIONS: This study demonstrates good long term survival rates after definitive radiotherapy for patients with nasopharyngeal carcinomas. Patients with advanced and lower neck disease have the highest risk of developing distant failures. Such patients can be considered the reference risk group to test the value of adjunctive chemotherapy.

Adolescent↗
PubMed1997

Peripheral nerve regeneration: the effects of postoperative irradiation.

The purpose of this study was to evaluate the effects of postoperative external cobalt-60 beam irradiation on nerve regeneration. Sixty-five 250-gm male Sprague-Dawley rats were studied. Peripheral nerve regeneration was measured by walking track analysis and histomorphology of the proximal, graft, and distal nerve segments. These 65 animals underwent a 1.5-cm interpositional nerve graft into the right posterior tibial nerve. The left leg served as a control. Each animal was then randomly allocated into one of four groups. Group 1 served as control. Groups 2 through 4 were subjected to external cobalt-60 gamma-ray irradiation through a 2.5-cm circular portal for a total fractionated dose of 30, 50, and 70 Gy beginning on postoperative day 3. Radiation was administered in 2-Gy fractions, 5 fractions per week, with a top-up dose of 16 Gy given at the end of the fractionated irradiation. Walking track analysis was performed at 30, 60, 90, and 120 days after nerve grafting. At the conclusion of 120 days, sections of the proximal, grafted, and distal nerve were harvested, stained, and examined histomorphologically. Hematoxylin and eosin stains also were obtained. Evaluation of the print-length index demonstrated no statistical difference between the unirradiated controls and the irradiated groups. The total number of axons per square millimeter and nerve fiber density per square millimeter were significantly decreased in the distal segment of all the irradiated groups when compared with controls. Despite the reduction in myelinated regenerating fibers, no reduction in function was observed, as measured by walking track analysis. We would therefore recommend immediate reconstruction of peripheral nerve defects in the face of postoperative irradiation.

Animals↗
PubMed1997

Magnetic resonance imaging of the central nervous system of the rhesus monkey.

The purpose of the study reported here was to document the ability of magnetic resonance imaging to depict the imaging characteristics of normal structures within the central nervous system of adult rhesus monkeys. The head and the cervical and thoracic parts of the spinal cord of two rhesus monkeys were imaged in a clinical 1.5-T whole-body imager. Specific images were selected, and some notable structures were identified. Results of this study document the usefulness of MRI as an expeditious, noninvasive research and diagnostic imaging technique and illustrates the normal magnetic resonance signal patterns of the brain and spinal cord in rhesus monkeys.

Animals↗
PubMed1997

Radiation therapy for nonmelanoma skin carcinomas.

Radiotherapy plays an important role in the management of appropriately selected skin carcinomas. Tumors of the eyelid, nose, and ear can be treated successfully with preservation of adjacent normal tissues. Tumors located in the embryologic fusion planes of the face can be irradiated with wide margins, either as primary or postoperative therapy. Radiotherapy has a significant role in the postoperative setting for patients with high-risk features in their pathologic specimens. Patients with NECS (Merkel cell carcinoma) have a high recurrence rate after surgical excision; these patients should undergo radiotherapy after resection of the clinically evident disease.

Basal Cell Carcinoma↗
PubMed1996

Does induction chemotherapy have a role in the management of nasopharyngeal carcinoma? Results of treatment in the era of computerized tomography.

PURPOSE: To assess the outcomes of patients with nasopharyngeal carcinoma (NPC) whose treatment was determined by computerized tomography (CT) and/or magnetic resonance imaging staging and to analyze the impact of induction chemotherapy and accelerated fractionated radiotherapy. METHODS AND MATERIALS: The analysis is based on 122 of 143 previously untreated patients with NPC treated with radiation therapy at The University of Texas M. D. Anderson Cancer Center between 1983 and 1992. Excluded were 4 patients treated with palliative intent, 4 children, 12 patients not staged with CT, and 1 patient who died of a cerebrovascular accident prior to completion of treatment. The stage distribution was as follows: AJCC Stage I-2, Stage II-7, Stage III-12, Stage IV-101; Tl-15, T2-33, T3-22, T4-52; N0-32, N1-10, N2-47, N3-32, Nx-1. Fifty-nine (48%) patients had squamous cell carcinoma; 63 (52%) had lymphoepitheliomas, undifferentiated NPC or poorly differentiated carcinoma, NOS (UNPC). Sixty-seven patients (65 with Stage IV disease) received induction chemotherapy. Fifty-eight patients (24 of whom had induction chemotherapy) were treated with the concomitant boost fractionation schedule. The median follow-up for surviving patients was 57 months. RESULTS: The overall actuarial 2- and 5-year survival rates were 78 and 68%, respectively. Forty-nine patients (40%) had disease recurrence. Thirty-three (27%) had local regional failures; 19 at the primary site only, 8 in the neck and 6 in both. Local failure occurred in 31% of patients staged T4 compared to 13% of T1-T3 (p = 0.007). Sixteen patients failed at distant sites alone. Among Stage IV patients the 5-year actuarial rates for patients who did and did not receive induction chemotherapy were as follows: overall survival: 68 vs. 56% (p = 0.02), freedom from relapse: 64 vs. 37% (p = 0.01), and local control: 86 vs. 56% (p = 0.009). The actuarial 5-year distant failure rate in patients with UNPC who were treated with induction chemotherapy and controlled in the primary and neck was 13%. In patients who did not receive chemotherapy, the actuarial 5-year local control rates for patients treated with concomitant boost or conventional fractionation were 66 and 67%, respectively. CONCLUSIONS: While not providing conclusive evidence, this single institution experience suggests that neoadjuvant chemotherapy for Stage IV NPC patients improves both survival and disease control. Recurrence within the irradiated volume was the most prevalent mode of failure and future studies will evaluate regimens to enhance local regional control.

Adolescent↗
PubMed1996

Comparison between normal tissue reactions and local tumor control in head and neck cancer patients treated by definitive radiotherapy.

PURPOSE: This study was conducted to test for the relationship between tumor and normal tissue radiosensitivity, by comparing local tumor control to the severity of acute and late normal tissue reactions in head and neck cancer patients treated by definitive radiotherapy. METHODS AND MATERIALS: Two hundred eighty-six patients with head and neck cancer who were treated at the University of Texas M. D. Anderson Cancer Center between 1983 and 1993 were selected for the study. Of these, 124 (43%) were treated by a concomitant boost regimen and 162 (57%) by hyperfractionation. All patients had at least 1 year of follow-up. The tumor stage distribution according to the 1992 American Joint Committee on Cancer (AJCC) staging system was as follows: T1, 3%; T2, 53%; T3, 40%; T4, 4%. The average doses delivered were 71.2 Gy and 76.2 Gy for the concomitant boost and hyperfractionation regimens, respectively, with no significant variation between patients. Acute and late reactions were recorded using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) grading system (0 to 4). The median follow-up period was 38 months (range: 12-107 months). The time to local tumor recurrence was analyzed in relation to the severity of acute and late reactions expressed as the maximum recorded grades, and to the time intensity of acute mucositis, expressed as the area under the curve of mucositis grade vs. time. Univariate and multivariate analyses also included T stage, N stage, and site of origin as other prognostic variables, and were carried out using a proportional hazards model. RESULTS: Fifty-four patients (19%) suffered local failure. T stage was found to significantly influence local control (p = 0.009). There was a nonsignificant trend for higher failure rates in patients with maximum Grade 1 or 2 vs. those with Grade 3 or 4 acute mucositis (28 and 18%, respectively; p = 0.17). No correlation was found between the severity of late reactions and local tumor control after radiotherapy. Analysis by time intensity of mucositis revealed a wide variation between individuals with a nonsignificant trend for higher local failure rates in patients with low mucositis time intensity scores. CONCLUSIONS: These clinical results suggest a possible relationship between normal tissue and tumor radiosensitivity. However, additional studies with a larger numbers of patients, and using refined normal tissue endpoints that incorporate a time function are needed to fully elucidate this question.

Acute Disease↗
PubMed1996

Radiation therapy for malignant melanoma.

Sufficient biologic and clinical evidence now exists to refute the longstanding dogma that melanomas are uniformly radiation resistant and hence radiation therapy has little role in the management of this disease. Although surgery remains the treatment of choice for the vast majority of localized melanomas, available data indicate that radiation therapy is a viable alternative for a few subsets of patients in whom surgery would result in cosmetic or functional deformity, such as patients with large facial lentigo maligna melanomas or small or intermediate-sized uveal melanomas. Retrospective and Phase II prospective studies have revealed that elective/adjunctive radiation therapy improves the local-regional control rate in patients with thick primary lesions, nodal involvement, or mucosal melanomas. However, the impact of elective/adjunctive radiation therapy on the survival rate has yet to be determined. Radiation therapy has been established as a simple and cost-effective treatment modality for palliation of patients with symptomatic metastatic spread. The response of metastatic deposits to radiation varies with the tumor volume, total dose, and dose per fraction. The choice of optimal fractionation depends on tumor site and the patient's survival expectation. New data indicate that hyperthermia enhances the response of metastatic lesions to radiation. Ongoing research with a variety of experimental strategies may offer the possibility of further increasing the utility of radiation therapy in the management of this disease.

Actuarial Analysis↗