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Biomedical subjects

L B Harrison

Publications and source records attributed to L B Harrison.

At least 73 records · Page 4Linked to original sources

Long-term treatment results of postoperative radiation therapy for advanced stage oropharyngeal carcinoma.

BACKGROUND: The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS: Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%). RESULTS: The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions. CONCLUSIONS: The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.

Adult↗

The indications for elective treatment of the neck in cancer of the major salivary glands.

To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982. Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors (P less than 0.00001). High-grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate-grade or low-grade tumors (P less than 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High-grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

Analysis of Variance↗

Induction chemotherapy for non-small cell lung cancer with clinically evident mediastinal node metastases: the role of postoperative radiotherapy.

Survival for clinical Stage IIIa (T1-3, N2) non-small cell lung cancer is very poor because of poor local disease control and systemic spread. To address these shortcomings, we initiated a treatment program with induction chemotherapy, surgery, and postoperative radiation reserved for patients with residual disease at thoracotomy. Between 1984 and 1986, 41 patients with clinically evident N2 disease were treated with induction chemotherapy followed by resection and the selective use of intraoperative brachytherapy. All patients with tumor in the resection specimen received two cycles of chemotherapy and 15 patients received radiation therapy. With a median follow-up of 5.4 years, overall survival is 27% at 3 years, and 12% at 5 years. Despite the adverse selection process median survival is 19 months for patients receiving postoperative radiation therapy, and 22 months for the more favorable patients not requiring radiation therapy, supporting the selective use of postoperative radiation in this setting. In summary, this treatment has yielded good median survival and long-term survival for some of the patients. However, the ultimate value of this approach can only be determined by prospective trials which compare it to standard therapy.

Adult↗

The importance of brachytherapy technique in the management of primary carcinoma of the vagina.

This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty-six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease.

Adult↗

Nasopharyngeal brachytherapy with access via a transpalatal flap.

We used a posteriorly based transpalatal flap for interstitial nasopharyngeal brachytherapy in five patients with nasopharyngeal carcinoma. All of these implants were done with iodine 125 seeds. The disease in three of five patients has been controlled locally for 27, 30, and 40 months, respectively. Two patients experienced local failure and died. There have been no palatal healing problems despite high doses of previous radiation in all of our patients. No palatal incompetence has been seen. This technique appears safe and should be considered for discrete lesions of the high posterior or superior nasopharynx that cannot be approached by less invasive methods.

Adult↗

Base-of-tongue cancer treated with external beam irradiation plus brachytherapy: oncologic and functional outcome.

Between January 1981 and June 1990, 36 previously untreated patients with squamous cancer of the base of the tongue were treated with radiation therapy. This therapy consisted of a 5,000-5,400-cGy external beam plus a 2,000-3,000-cGy boost to the base of the tongue with an iridium-192 implant. Necks with negative nodes were only irradiated, while necks with positive nodes were treated with irradiation plus neck dissection. Actuarial local control and survival at 2 years were 87.5%. Neck control was achieved in 35 of 36 patients. When implantation was performed with the nonlooping technique, the injury rate was statistically higher than in patients who underwent implantation with the looping technique (P = .02). Thirty patients participated in a function assessment involving a Performance Status Scale for patients with head and neck cancer. The authors concluded that management of base-of-tongue cancer with external beam irradiation plus brachytherapy is both oncologically and functionally successful.

Adult↗

Current status of larynx preservation with multimodality therapy.

Patients with advanced squamous cell carcinoma of the head and neck often require total laryngectomy, but many patients will refuse the procedure despite the prospect of a lower cure rate. Radiation therapy alone can cure selected patients. Chemotherapy has been combined with radiation in a variety of ways, in hopes of improving local control, preserving function, and achieving survival better than that achieved with radiation therapy alone. Several studies have yielded encouraging results, including the only randomized study that has compared chemotherapy/radiation to standard total laryngectomy and postoperative radiation therapy. All function preservation treatment programs require a motivated and compliant patient, careful patient monitoring, and close cooperation among surgical, radiation, and medical oncologists.

Carcinoma, Squamous Cell↗

Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors.

Thirty-eight histologically confirmed desmoid tumors were treated with conservative surgical resection and interstitial iridium 192. Patients included in this series constituted a poor prognostic group. Seventy five percent (75%) had previous recurrences of their disease and 50% had tumors 8 cm or greater in size. In addition, 16% of the patients had gross residual disease after surgical excision and 79% had positive or close margins of resection. With a median follow-up of 5.5 years, the 5-year actuarial in-field local control rate was 75% and the overall local control rate was 66%. Four of the 12 local recurrences developed at the periphery of the implant volume and four patients failed at least 3 cm or more beyond the treated volume. After salvage therapy, the 5-year actuarial local control rate was 95%. Two patients required amputation for recurrent disease. Thirty of 34 patients remain free of disease with an excellent functional result achieved. The authors conclude that surgical resection and postoperative interstitial iridium 192 is effective therapy for patients with desmoid tumors. Despite the fact that most patients in this series had bulky, recurrent tumors, excellent long-term local control and limb function were achieved.

Adolescent↗

Paraspinal tumors: techniques and results of brachytherapy.

Because of their proximity to nerve roots and the spinal cord, it is frequently difficult to achieve complete resection of paraspinal tumors. We have used brachytherapy in an attempt to prevent local recurrence and its associated neurological sequelae. This report analyzes our experience with 35 patients to determine the feasibility, optimal techniques, and efficacy of this approach. The tumor types were non small-cell lung cancer (18), sarcomas (9), and other tumor types (8). Temporary, single plane implants using Ir-192 (median minimum peripheral dose 3000 cGy) were used in 21 patients, and permanent I-125 implants were used in 14 cases (median matched peripheral dose 12,500 cGy). Local control was achieved in 51% (18/35). However, local control was poor when lung cancers were implanted and in cases where the dura was exposed. Radiation myelitis did not occur despite the combined effects of previous external beam radiotherapy (N = 21) and brachytherapy. Our experience demonstrates that combined surgery and paraspinal brachytherapy can be performed with acceptable toxicity and is reasonably effective in preventing local relapse and its neurologic sequelae, particularly for tumors other than lung cancers.

Brachytherapy↗

Improved dose distributions for 3D conformal boost treatments in carcinoma of the nasopharynx.

This study was designed to demonstrate the feasibility of 3-dimensional (3D) treatment planning in patients with carcinoma of the nasopharynx, and to explore its potential therapeutic advantage over the traditional 2-dimensional (2D) approach in this disease. Qualitative and quantitative comparisons between the two techniques were made for the boost portion of the treatment (19.8 Gy of a total 70.2 Gy treatment schedule) in 10 previously untreated patients and for the entire treatment in 5 patients with locally recurrent disease. The 2D and 3D plans were compared in each patient using dose-volume histograms (DVH's), tumor control probabilities (TCP's), normal tissue complication probabilities (NTCP's), and a new biologic figure of merit that describes the probability of uncomplicated control. Although there was no attempt to optimize the 3D treatment approach by using this method throughout the total treatment course (rather than for the boost only), it was still found that for each of the endpoints examined the 3D approach resulted in improved plans. An average of 22% of the target volume was underdosed at the 95% isodose level with the 2D plans compared to 7% with the 3D plans. The improved treatment planning by 3D increased the mean dose to the tumor volume by an average of 13% over 2D planning. The dose to normal structures such as the mandible and parotid glands was reduced with the 3D plans while the brain stem and spinal cord remained within tolerance limits. The probability of uncomplicated tumor control was increased by an average of 15% with 3D treatment planning compared to the 2D approach. Our findings demonstrate the potential of 3D planning for improving the treatment of carcinoma of the nasopharynx, but prospective studies are required to define the true clinical advantages of this methodology.

Humans↗

Twice daily thoracic irradiation for limited small cell lung cancer.

Thoracic failure is a significant obstacle to the cure of limited stage small-cell lung cancer (LSCLC) patients treated with combined modality therapy. In 1985 we initiated a prospective trial to evaluate the impact of twice daily thoracic irradiation without concomitant chemotherapy on control of intrathoracic tumor in LSCLC. Twenty-nine patients treated in this fashion were compared with 36 patients treated from 1979-1982 with once daily thoracic irradiation and concomitant chemotherapy. Both groups received the same induction chemotherapy; cyclophosphamide, Adriamycin, and vincristine (CAV) alternating with cisplatin and etoposide. For consolidation, the twice daily patients received thoracic irradiation, 45 Gy in 1.5 Gy fractions given twice daily, and the once daily patients received thoracic irradiation, 45 Gy in 2.5 Gy fractions given once daily with concomitant cyclophosphamide and vincristine. After completion of radiotherapy both groups received maintenance chemotherapy. The complete response (CR) rate after thoracic irradiation was higher for twice daily patients (86% (25/29) compared to the once daily patients [61% (22/36), p = 0.02]. However, this advantage was offset by the shorter duration of thoracic control among CR patients treated with twice daily thoracic irradiation compared to once daily thoracic irradiation (32% vs 67% at 2 years, p less than 0.05). In view of the enhanced initial response of LSCLC to twice daily thoracic irradiation, this basic radiotherapeutic approach seems appropriate, but new strategies using higher doses of twice daily thoracic irradiation or concomitant chemotherapy appear to be necessary to enhance long-term thoracic control.

Carcinoma, Small Cell↗

Radiation therapy for unresectable rectal cancer.

The standard approach to patients with unresectable rectal cancer is pre-op radiation therapy followed by surgery. To determine the impact of RT on local failure and survival, we present an analysis of our preliminary results of this approach in patients with unresectable rectal cancer. A total of 22 patients were analyzed (9 primary, 13 recurrent). The median follow-up was 22 months. There were two groups of patients. Group 1 included 12 patients with unresectable tumors in whom surgery was planned following pre-operative radiation therapy. Group 2 included 10 patients in whom no surgery was planned following radiation therapy due to extensive pelvic bone destruction. The whole pelvis received 4680 cGy followed by a boost of 360-1440 cGy. Six underwent brachytherapy. For the total patient group, the 3-year actuarial survival was 52% (Group 1: 91% vs Group 2: 30%). Patterns of failure as a component of failure were: local failure (or local progression): 50%, abdominal: 23%, and distant: 9%. The dose of pelvic radiation had no significant impact on the local failure rate (5040 cGy: 55% vs greater than 5700 cGy:45%). None of the seven patients with negative margins developed local failure compared with 73% of those with positive margins. The complete resection rate in Group 1 patients was 58%, and all are alive without local failure. Further follow-up will be needed to determine the ultimate local failure and survival rates.

Adult↗

Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb.

The treatment of soft tissue sarcoma of the limb by function-saving resection and brachytherapy (BRT) was systematically studied from 1975 to 1990 at the Memorial Sloan-Kettering Cancer Center, using iridium-192 temporary tumor-bed implants. Initial experiences showed an 88% local control rate in 33 patients who had locally advanced sarcomas, many of which would have required treatment by amputation. The technique also controlled 70% of tumors that abutted or invaded a major neurovascular bundle that was dissected out and preserved. A prospective randomized study (BRT vs no BRT) confirmed the highly significant efficacy of BRT in preventing local recurrence. This salutary effect is mainly seen in high-grade tumors. Major complications of wound healing occurred in the earlier years of this experience. Adoption of improved techniques of surgical wound repair, standardization of radiation dose planning, and in particular, postponing the loading of radiation sources until after the fifth postoperative day has reduced the rate of serious wound complications, to a level not significantly different from that seen after surgical resection alone. These results rival those currently achieved in centers experienced in external beam therapy of soft tissue sarcomas, and offer the advantage of completion of treatment in one relatively short hospital stay.

Amputation, Surgical↗

Concomitant chemotherapy-radiation therapy followed by hyperfractionated radiation therapy for advanced unresectable head and neck cancer.

In January 1988, we initiated a prospective study evaluating a new treatment approach with chemotherapy and radiotherapy for unresectable head and neck cancer. Weeks 1-4 were the initial debulking phase. Radiotherapy was delivered using 1.8 Gy/day to large portals including gross disease and all areas at risk. Cisplatinum, 100mg/m2, was given concomitant with radiotherapy on days 1 and 22. Weeks 5 and 6 were the boosting phase. This involved twice-a-day irradiation. The AM fraction of 1.8 Gy was given to the entire area at risk, whereas the PM dose of 1.6 Gy was limited to the gross disease alone. Thus a total of 70 Gy/6 weeks was delivered. A total of 24 patients were treated, 22 of whom have completed this protocol and are evaluable. All patients had massive disease, with 15 having gross involvement of brain, orbit, skull base, or carotid artery. Follow-up ranged from 3-22 months (median 12 months). Major responses were achieved in 96%, with 64% complete responses and 32% partial responses. Two patients with PR were able to undergo complete surgical resection, making the overall rate of complete response, including surgery, 73%. At 1 year, actuarial survival was 69%, and local progression-free survival was 56%. Distant metastases developed in 5 (23%). This approach appears both safe and effective in producing excellent regression and local control for far advanced head and neck cancer. More time is needed to see if these results are sustained. Efforts to build upon this experience appear warranted.

Adenocarcinoma↗

The role of multimodality therapy in soft-tissue sarcoma.

Soft-tissue sarcomas are uncommon malignancies. The development during a period of 8 years, in one institution, of a prospective data base incorporating more than 1600 patients with these tumors is described. The most common sites for occurrence are the extremities, but they can occur in any of the soft tissues of the body. Liposarcoma and leiomyosarcoma are the most common histopathologic conditions identified. Prognostic factors for both recurrence and survival include site, histopathology, size, grade, and adequacy of resection. A prospective randomized trial of the use of adjuvant radiation by the brachytherapy technique in extremity lesions has shown a decrease in local recurrence, but no impact on survival. Eligible patients not randomized to the trial show no difference in local recurrence or survival, regardless of whether they received adjuvant radiation.

Adolescent↗