Scaling exponents of forced polymer translocation through a nanopore.

We investigate several properties of a translocating homopolymer through a thin pore driven by an external field present inside the pore only using Langevin Dynamics (LD) simulations in three dimensions (3D). Motivated by several recent theoretical and numerical studies that are apparently at odds with each other, we estimate the exponents describing the scaling with chain length (N) of the average translocation time , the average velocity of the center of mass , and the effective radius of gyration during the translocation process defined as approximately Nalpha, approximately N(-delta), and Rg approximately Nnu respectively, and the exponent of the translocation coordinate (s-coordinate) as a function of the translocation time approximately tbeta. We find alpha = 1.36 +/- 0.01, beta = 1.60+/- 0.01 for approximately taubeta and beta = 1.44 +/- 0.02 for approximately taubeta, delta = 0.81 +/- 0.04, and nu congruent with nu = 0.59 +/- 0.01, where nu is the equilibrium Flory exponent in 3D. Therefore, we find that approximately N1.36 is consistent with the estimate of approximately /. However, as observed previously in Monte Carlo (MC) calculations by Kantor and Kardar (Y. Kantor, M. Kardar, Phys. Rev. E 69, 021806 (2004)) we also find the exponent alpha = 1.36 +/- 0.01 < 1 + nu. Further, we find that the parallel and perpendicular components of the gyration radii, where one considers the "cis" and "trans" parts of the chain separately, exhibit distinct out-of-equilibrium effects. We also discuss the dependence of the effective exponents on the pore geometry for the range of N studied here.

Small lymphocytic lymphoma.

The clinical course of 54 patients with small lymphocytic lymphoma (SL) was reviewed. The majority of patients had disseminated lymphoma at the time of diagnosis; 14 patients (26%) presented with Ann Arbor stage I and II disease. Five- and 10-year survival for all patients was 76% and 49%. The only clinicopathologic features identified that predicted a shortened survival were the presence or absence of systemic (B) symptoms (15% v 63% at 10 years, P = .01) and a diffuse rather than pseudofollicular nodal architecture (47% v 87% at 10 years, P = .04). Initial bone marrow involvement was not an adverse prognostic factor for patients who presented with stage III and IV disease. Ten patients developed a marked lymphocytosis consistent with progression to a leukemic phase (chronic lymphocytic leukemia [CLL]). These ten patients had a median initial lymphocyte count of 2,790, compared with 1,580 for those patients who did not progress to CLL (P = .0001). Developing CLL did not adversely affect survival (P = .48). Thirty-seven patients were treated with various combinations of radiation and chemotherapy; 17 patients received no initial therapy. Ten-year freedom from relapse (FFR) for stage I and II patients treated with irradiation was 80% and 62%; FFR for stage III and IV treated patients was 11%. Despite the marked differences in FFR, no statistically significant difference in survival could be demonstrated between the various stages. Selected patients with advanced SL received no initial therapy; these patients had a 10-year survival that was not statistically different from the immediately treated stage III and IV patients. Patients with stage I and II SL should be treated with irradiation; prolonged FFR and possibly cure of the disease can be achieved in these patients.

Effectiveness of combined induction chemotherapy and radiotherapy in advanced nasopharyngeal carcinoma.

PURPOSE: This prospective trial was conducted with the goal of achieving an improvement in both overall and progression-free survival in previously untreated patients with stage IV nasopharyngeal carcinoma who received an induction chemotherapy regimen of fluorouracil (5-FU) and cisplatin followed by radiotherapy. PATIENTS AND METHODS: From January 1985 to January 1990, 47 patients with T1-4N2-3M0 squamous cell carcinoma of the nasopharynx were treated at The University of Texas M.D. Anderson Cancer Center with two to three cycles of 5-FU (1,000 mg/m2 continuous infusion per day x 5 days) plus cisplatin (100 mg/m2 continuous infusion on day 1 only) followed by radiotherapy using the conventional time/dose schedule. RESULTS: The response rate to chemotherapy was 93.2% (20.5% complete response [CR]; 72.7% partial response [PR]), and the overall CR rate after radiotherapy was 86%. With a median follow-up period of 53 months, the 2-, 4-, and 6-year survival rates were 80%, 71.6%, and 67.4%; the overall treatment failure rate was 27%. Treatment was well tolerated and without significant acute or chronic toxic effects. CONCLUSION: The results of this prospective study demonstrate that 5-FU plus cisplatin followed by radiotherapy can induce a durable remission in a high proportion of patients with poor-prognosis stage IV nasopharyngeal carcinoma.

Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: toxicities and responses.

PURPOSE: Extrapolating from our experience delivering a "boost" field of radiation concurrently with fields treating both gross and subclinical disease at the end of a course of radiation therapy, we developed a regimen to deliver concurrent chemotherapy during the last 2 weeks of a conventionally fractionated course of radiation. PATIENTS AND METHODS: Patients had stage III or IV biopsy-proven squamous cell carcinoma originating from a head and neck mucosal site. The regimen was 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisplatin given daily with each radiation dose during the last 2 weeks. A phase I study was performed to determine the maximum-tolerated dose (MTD) before a phase II study was conducted. RESULTS: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day for cisplatin. Mucositis persisting more than 6 weeks after therapy was the dose-limiting toxicity. A total of 60 patients were treated on the two phases of the study. Eighteen patients (35%) treated at the MTD developed prolonged mucositis. There were two cases of neutropenic sepsis, including one fatality. The actuarial 2-year rates for overall survival, freedom from relapse, and local control were 62%, 59%, and 80%, respectively. CONCLUSION: Preliminary locoregional control rates seem to be higher than those reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliver an intense treatment schedule, which could be completed without significant interruptions, and to obtain high control rates above the clavicles. These end points were achieved.

Neurocognitive effects of therapeutic irradiation for base of skull tumors.

PURPOSE: To determine whether radiation therapy delivered to the paranasal sinuses causes any long-term impairment in neurocognitive function as a result of incidental brain irradiation. METHODS AND MATERIALS: Nineteen patients who received paranasal sinus irradiation at least 20 months and up to 20 years before assessment were given a battery of neuropsychologic tests of cognitive function. Radiation was delivered by a three-field (one anteroposterior and two lateral) technique. The median radiation dose was 60 Gy (range 50-68 Gy) in fractions of 1.8 to 2 Gy. The volume of irradiated brain was calculated from planning computed tomography slices or simulation films. The results of the neuropsychologic tests were compared to normative control values. RESULTS: Memory impairment was found in 80% of the patients, and one-third manifested difficulty with visual-motor speed, frontal lobe executive functions, and fine motor coordination. Two of the patients had frank brain necrosis with resultant dementia and blindness, and three had evidence of brain atrophy. Three of the fourteen patients without documented cerebral atrophy or necrosis were disabled from their normal activities. Three patients also developed pituitary dysfunction. Neurocognitive symptoms were related to the total dose of radiation delivered but not to the volume of brain irradiated, side of radiation boost, or chemotherapy treatment. The pattern of test findings was consistent with radiation injury to subcortical white matter. CONCLUSIONS: Radiation therapy for paranasal sinus cancer may cause delayed neurocognitive side effects. Currently, however, the development of severe adverse effects appears to be decreasing because of improvements in the techniques used to deliver radiation. Lowering the total dose and improving dose distributions should further decrease the incidence of delayed brain injury due to radiation.

Dosimetric evaluation of total scalp irradiation using a lateral electron-photon technique.

PURPOSE: To evaluate the radiation dosimetry of a new technique for total scalp irradiation. METHODS AND MATERIALS: A treatment technique described by Akazawa (1989) has been studied. During each fraction, two electron and two photon fields are treated. While most of the lateral scalp is treated with the electron fields, a rind of scalp close to the midsagittal plane is irradiated by parallel-opposed lateral photon fields. A wax bolus is used to build up skin dose and to protect the brain from electron dose. The dose distribution and dose-volume histograms were evaluated for different field arrangements using a 3-dimensional treatment planning system. After modifying the technique, in-vivo thermoluminescent dosimetry were used to evaluate the dose distributions for the first two patients. RESULTS: To compensate for the lack of dose from the opposed photon field at the junction, the technique was modified using overlapped fields instead of abutting fields. A field overlap of 3 to 4 mm between the electron and photon fields was found optimal. When used with the field junction shift of 1 cm midway through the treatment, this scheme resulted in a dose uniformity of -5% to +15% of the prescribed dose in the region of abutment. Results of the 3-dimensional dose calculation were supported by in-vivo thermoluminescent dosimetry on two patients. CONCLUSION: On the basis of computer dose calculations and in-vivo dosimetry. Akazawa's technique for scalp irradiation can be improved by using a 3 to 4 mm overlap of electron and photon fields. This modified technique is practical and produces clinically acceptable dosimetry.

Hyperfractionated radiation in the treatment of squamous cell carcinomas of the head and neck: a comparison of two fractionation schedules.

PURPOSE: In 1984 we began treating patients with squamous cell carcinomas of the larynx and hypopharynx with hyperfractionated radiotherapy. Patients received 76.8 Gy in 1.2 Gy fractions twice daily, with a 4 h interfraction interval. In 1988, this schedule was modified in patients treated with shrinking field techniques. The dose per fraction was slightly reduced (while not changing the total dose), and the interfraction interval was increased to 6 h. The goal was to decrease toxicity while maintaining satisfactory local-regional control. This retrospective study analyzes the results of this schedule modification. METHODS AND MATERIALS: Two hundred thirty-six patients were included in the analysis. Distribution of patients by primary site and T stage was as follows: supraglottic larynx, 120 patients; hypopharynx, 70; true vocal cord, 24; and oropharynx, 22; T1, 5 patients; T2, 118; T3, 93; T4, 19; and Tx, 1. Ninety-nine patients presented with cervical nodal disease. Seventy-eight patients (group A), including 16 treated with induction chemotherapy, were treated throughout with 1.2 Gy fractions twice daily and a 4-h interfraction interval. Subsequently, 158 patients (group B), 57 of whom received chemotherapy, received 1.1 Gy fractions to 55 Gy, and then 1.2 Gy fractions to their boost volumes to 76.6 Gy. The interfraction interval was 6 h. Median follow-up was 91 and 35 months for group A and B, respectively. RESULTS: Two-year actuarial survival, local control, and ultimate local rates were 70%, 75%, and 85%, respectively. Differences between survival rates for group A and group B were not statistically significant, with 2-year rates of 66% and 72%, respectively. Overall local control rates at 2 years were 77% and 74%, respectively, for groups A and B (p = 0.22). However, there was a trend toward inferior results in group B patients with T3 disease (67% at 2 years compared to 76% in group A, p = 0.13). Confluent mucositis and persistent mucositis developed in 52% and 14% of group A patients, but only 37% and 4% of group B patients (p = 0.02 and p < 0.01, respectively). There was a near significant trend toward fewer late complications in group B who developed an 8% complication rate at 3 years compared to 15% of group A patients (p = 0.07). CONCLUSIONS: The net effect of reducing the dose per fraction to 1.1 Gy twice daily for fields covering gross disease and subclinical sites, and increasing the interfraction interval to 6 h was to reduce the incidence of both acute and late complications. Excellent overall local control rates (85%) for T2 lesions were achieved with both hyperfractionation regimens and we, therefore, continue to treat patients with T2 tumors with the modified schedule. The overall results in selected patients with T3 lesions was also satisfactory (69%), but as there was a trend towards poorer local control in patients treated with 1.1 Gy fractions, we recommend using 1.2 Gy for the entire treatment of these patients, while maintaining the 6 h interfraction interval to reduce the risk of late complications.

The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.

PURPOSE: Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. METHODS AND MATERIALS: Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. RESULTS: Twenty-three patients (12%) had local recurrences with 5-, 10-, and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. CONCLUSIONS: Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking.

The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma.

Between 1966 and 1987, 54 patients with non-disseminated Merkel cell carcinoma (MCC) were treated with curative intent at the University of Texas M. D. Anderson Cancer Center. The primary tumor site was in the head and neck in 38 patients. The majority of the patients (57%) were referred with locoregionally recurrent disease. For the whole group, survival was 30% after 5 years. Patients who presented with nodal involvement had a median survival of 13 months compared with 40 months for node-negative patients (p less than .04). Only 4/37 patients treated initially by surgery alone were locoregionally controlled, with a median time to recurrence of 4.9 months. Salvage with radiation therapy was attempted in 18 patients (after additional surgery in 14), but was successful in only four. The predominant failure pattern in this subgroup was distant metastases, occurring as a component of initial recurrence in 12/18 patients. Prior to 1982, the philosophy of initial therapy was to give postoperative irradiation only to patients with large primaries or nodal involvement. Subsequently, postoperative radiotherapy has been recommended routinely, and all five patients treated with this approach remain disease-free. In total, 31 patients (including 10 patients with gross disease) were irradiated at M. D. Anderson; only one developed an in-field locoregional recurrence as an initial site of failure. However, three marginal recurrences occurred. The median dose to the primary tumor, first echelon nodes, and supraclavicular nodes was 60, 51, and 50 Gy, respectively. Our current recommendation for initial treatment is excision of the primary tumor followed by irradiation with generous fields to include the primary tumor site and draining regional lymphatics to doses of 46-50 Gy in 2 Gy fractions. For gross unresected disease, 56-60 Gy is recommended. The role of adjuvant systemic therapy remains to be defined.

Concomitant boost radiotherapy schedules in the treatment of carcinoma of the oropharynx and nasopharynx.

Concomitant boost schedules are characterized by delivering the boost (10-12 fractions) as second daily treatments during rather than following the basic wide field irradiations. This results in shortening the overall time to administer 69-72 Gy from 7 1/2-8 weeks to 6 weeks, which we hoped would improve the tumor control rate by reducing the opportunity for tumor clonogens to regenerate during treatment. From August 1985 to August 1988, 79 patients with T2-4 carcinomas of the oropharynx (72 patients) or nasopharynx (7 patients) were treated according to 1 of the 3 variants of the concomitant boost technique. The median age of patients was 60 years (range: 19-84 years) and the male-to-female ratio was 2.6. The overall 2-year actuarial primary and nodal control rates by radiotherapy alone were 74% and 76%, respectively. The ultimate 2-year control rates after surgical salvage were 82% and 84%, respectively. If the boost given during the last 2-2 1/2 weeks of basic treatment, a slightly better primary control rate (p = 0.11) resulted than if the boost was delivered during the first 2-2 1/2 weeks or twice a week throughout the basic treatment. The 2-year actuarial primary control rate of the 13 patients receiving induction chemotherapy prior to radiotherapy was significantly lower than that of patients treated with radiation only (81% vs 34%, p = 0.01), but this could be partly attributed to a more advanced stage in the chemotherapy group. The acute mucosal reactions were, as expected, more severe than those observed with conventional fractionation. Fifty patients developed confluent mucositis covering more than half of the boost area. Such reactions lasted for more than 6 weeks in seven patients. Late complications, however, so far observed, have been few. Three patients experienced chronic mucosal tenderness, 1 chronic mucosal ulceration, 2 transient bone exposure, and 1 carotid rupture following salvage surgery. The results so far appear to be better than the outcome of conventional radiotherapy. Its real value will be determined in a prospective randomized study.

Can positron emission tomography improve the quality of care for head-and-neck cancer patients?

PURPOSE: Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is a functional imaging modality that measures the relative uptake of 18FDG with PET. The purpose of this review is to assess the potential contribution of FDG-PET scans to the treatment of head-and-neck cancer patients. METHODS AND MATERIALS: Data were assessed from the literature with attention to what additional information may be gained from the use of FDG-PET in four clinical settings: (1) detection of occult metastatic disease in the neck, (2) detection of occult primaries in patients with neck metastases, (3) detection of synchronous primaries or metastatic disease in the chest, and (4) detection of residual/recurrent locoregional disease. RESULTS: Although the data are somewhat conflicting, FDG-PET appears to add little additional value to the physical examination and conventional imaging studies (supplemented by biopsy when appropriate) for the detection of subclinical nodal metastases, unknown primaries, or disease in the chest. However, FDG-PET scans are quite useful in differentiating residual/recurrent disease from treatment-induced normal tissue changes. A positive FDG-PET scan at 1 month after radiotherapy is highly indicative of the presence of residual disease, and a negative scan at 4 months after treatment is highly predictive of tumor eradication. CONCLUSIONS: Large-scale studies using newer generation equipment and more defined methods are needed to more rigorously assess the potential of FDG-PET in the detection of subclinical primary or simultaneous secondary tumors and of nodal or systemic spread. Currently, however, FDG-PET can contribute to the detection of residual/early recurrent tumors, leading to the timely institution of salvage therapy or the prevention of unnecessary biopsies of irradiated tissues, which may aggravate injury.

Postoperative radiotherapy for malignant tumors of the submandibular gland.

PURPOSE: This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. METHODS AND MATERIALS: Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). RESULTS: Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). CONCLUSIONS: High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years.

Hyperfractionated radiotherapy in the treatment of squamous cell carcinomas of the supraglottic larynx.

From January 1984 through December 1987, 41 patients with squamous cell carcinomas of the supraglottic larynx were treated with hyperfractionated radiotherapy at The University of Texas M. D. Anderson Cancer Center. Two patients had T1 primary tumors, 23 had T2, 15 had T3, and 1 had T4; 29 patients had no clinical evidence of nodal disease in the neck, 4 had N1, 5 had N2, and 3 had N3. Radiotherapy was delivered in 120 cGy fractions twice per day, with at least 4 hr between treatments. Total doses ranged from 7200 to 7900 cGy (median, 7680 cGy). Three patients had planned neck dissections before or after radiotherapy, and three patients with fixed vocal cord lesions were treated with preradiation chemotherapy. At the time of analysis, median follow-up was 22 months. Four patients have had failures at the primary tumor site. There has been one recurrence in the neck in a patient who also had a recurrence at the primary site. Three of the four patients with recurrences have been successfully treated with salvage surgery. Exclusive of surgical salvage, the actuarial disease-free local control rates above the clavicles in the 38 patients with T2 and T3 cancers were 96% at 1 year and 87% at 2 years. In comparison, the rates were 82% and 76% for a group of 98 patients with T2 and T3 lesions treated at this institution from 1970 to 1981 with 6500-7000 cGy given in 200 cGy fraction per day. As predicted, acute reactions were more severe but late complications were not increased in patients who received hyperfractionated radiotherapy compared with those treated by conventionally fractionated therapy. Only two patients have developed severe late complications one of whom required laryngectomy. Hyperfractionated radiotherapy appears to provide improved local control with a similar incidence of late complications when compared with conventionally fractionated therapy. To further improve the therapeutic ratio, our current protocol has been amended by reducing the large field dose per fraction to 110 cGy (with a 2 day protraction of overall time) and requiring a minimum interfraction interval of 6 hr.

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.

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.

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.

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.

Base-of-tongue carcinoma: treatment results using concomitant boost radiotherapy.

PURPOSE: To evaluate the efficacy of accelerated fractionated radiotherapy using the concomitant boost schedule for patients with squamous cell carcinoma of the base of tongue. METHODS AND MATERIALS: Between September 1984 and July 1992, 54 patients with squamous carcinoma of the base of tongue were treated at The University of Texas M. D. Anderson Cancer Center using the concomitant boost schedule. The distribution of T and N stages was T1-4, T2-27, T3-22, and T4-1; N0-9, N1-11, N2-24, N3-7, and NX-3. American Joint Committee on Cancer (AJCC) stage groupings were II-6, III-14, and IV-34. Before radiation, nodal excision and neck dissection were done in 5 and 10 patients, respectively; 5 patients had neck dissections after radiotherapy. Standard on and off spinal cord fields were irradiated with 1.8 Gy fractions to 54 Gy given over 6 weeks. The boost was given concomitantly during the large field treatment as a second daily (1.5 Gy) fraction, with an interfraction interval of 4-6 h. The median dose to the primary tumor was 72 Gy (range, 66-74 Gy). The median treatment duration was 42 days (range, 39-48 days). Only three patients had treatment interrupted for more than one scheduled treatment day. RESULTS: The 5-year actuarial overall survival and disease-specific survival rates were 59 and 65%, respectively, with a median follow-up of 41 months. The 5-year actuarial locoregional control rate was 76%. The actuarial local control rates achieved with radiotherapy at 5 years for T1, T2, and T3 primary tumors were 100%, 96%, and 67%, respectively; including surgical salvage, the local control rate of T3 primary tumors was 70%. Six patients had regional failures, which in three patients occurred in conjunction with primary tumor recurrence. Twenty-six patients with regional adenopathy were treated with radiation alone to full dose and had a complete clinical response in the neck; no planned neck dissections were performed in these patients. Only 2 of these 26 patients had subsequent regional failures. The 5-year actuarial risk of distant metastases in patients whose disease was controlled locoregionally was 21%. Grade 3 or 4 confluent acute mucositis occurred in 94% of patients. However, late complications were limited to two cases of transient mandibular exposure and three cases of self-limited mucosal ulcerations. CONCLUSION: The concomitant boost fractionation schedule is a very effective regimen for this disease when appropriately selected patients are treated with meticulous technique. The therapeutic ratio is favorable, with a high rate of disease control and no persistent severe late complications. Patients whose neck disease responds completely to treatment with this schedule do not appear to need a planned neck dissection.

Water bolus for electron irradiation of the ear canal.

PURPOSE: To demonstrate that water bolus in the external ear can decrease the dose inhomogeneity caused by auricular surface irregularities when the ear is in an electron-beam field. METHODS AND MATERIALS: Three-dimensional (3D) dose distributions with and without water bolus in the external ear were calculated for a representative patient. The electron dose calculations were made using the Hogstrom pencil beam algorithm as implemented in 3D by Starkschall. To demonstrate the use of water bolus in the ear clinically, the case of a patient with squamous carcinoma of the concha who was treated with electrons is presented. RESULTS: Water bolus markedly lessens the dose heterogeneity caused by the surface irregularities of the ear and the air in the external auditory canal. In the test case, the maximum dose was reduced by 25% using this technique. CONCLUSION: When the ear is in an electron beam field, warm water should be placed in the external auditory canal and concha. This maneuver may reduce the incidence of auricular complications that occur after electron-beam therapy.

Dosimetric evaluation of lead and tungsten eye shields in electron beam treatment.

PURPOSE: The purpose of this study is to report that commercially available eye shields (designed for orthovoltage x-rays) are inadequate to protect the ocular structures from penetrating electrons for electron beam energies equal to or greater than 6 MeV. Therefore, a prototype medium size tungsten eye shield was designed and fabricated. The advantages of the tungsten eye shield over lead are discussed. METHODS AND MATERIALS: Electron beams (6-9 MeV) are often used to irradiate eyelid tumors to curative doses. Eye shields can be placed under the eyelids to protect the globe. Film and thermoluminescent dosimeters (TLDs) were used within a specially constructed polystyrene eye phantom to determine the effectiveness of various commercially available internal eye shields (designed for orthovoltage x-rays). The same procedures were used to evaluate a prototype medium size tungsten eye shield (2.8 mm thick), which was designed and fabricated for protection of the globe from penetrating electrons for electron beam energy equal to 9 MeV. A mini-TLD was used to measure the dose enhancement due to electrons backscattered off the tungsten eye shield, both with or without a dental acrylic coating that is required to reduce discomfort, permit sterilization of the shield, and reduce the dose contribution from backscattered electrons. RESULTS: Transmission of a 6 MeV electron beam through a 1.7 mm thick lead eye shield was found to be 50% on the surface (cornea) of the phantom and 27% at a depth of 6 mm (lens). The thickness of lead required to stop 6-9 MeV electron beams is impractical. In place of lead, a prototype medium size tungsten eye shield was made. For 6 to 9 MeV electrons, the doses measured on the surface (cornea) and at 6 mm (lens) and 21 mm (retina) depths were all less than 5% of the maximum dose of the open field (4 x 4 cm). Electrons backscattered off a tungsten eye shield without acrylic coating increased the lid dose from 85 to 123% at 6 MeV and 87 to 119% at 9 MeV. For the tungsten eye shield coated with 2-3 mm of dental acrylic, the lid dose was increased from 85 to 98.5% at 6 MeV and 86 to 106% at 9 MeV. CONCLUSION: Commercially available eye shields were evaluated and found to be clearly inadequate to protect the ocular structures for electron beam energies equal to or greater than 6 MeV. A tungsten eye shield has been found to provide adequate protection for electrons up to 9 MeV. The increase in lid dose due to electrons backscattered off the tungsten eye shield should be considered in the dose prescription. A minimum thickness of 2 mm dental acrylic on the beam entrance surface of the tungsten eye shield was found to reduce the backscattered electron effect to acceptable levels.