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Biomedical subjects

L B Harrison

Publications and source records attributed to L B Harrison.

At least 55 records · Page 3Linked to original sources

Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation.

PURPOSE: To evaluate the feasibility and efficacy of a strategy using induction chemotherapy followed by radiation therapy (RT) as a means of organ-function preservation in patients with advanced oropharynx cancer. PATIENTS AND METHODS: From January 1983 to December 1990, 33 patients with advanced squamous cell oropharynx cancer whose appropriate surgical management would have required a tongue procedure and potential total laryngectomy were treated with one to three cycles of cisplatin (CDDP)-based induction chemotherapy. Patients with a complete response (CR) or partial response (PR) at the primary site then received definitive external-beam RT with or without interstitial implant with or without neck dissection with surgery to the primary tumor site reserved for disease persistence or relapse; patients with less than a PR after chemotherapy had appropriate surgery and postoperative RT recommended. RESULTS: With a median follow-up period of 6.2 years, actuarial overall and failure-free survival rates at 5 years are 41% and 42%, respectively. Chemotherapy toxicity contributed to the death of two patients and was possibly a factor in two others. Local control was achieved in 14 patients (42%) without any surgery to the larynx or tongue. Among 13 patients currently alive, all had a preserved larynx and only one required tongue surgery; 12 of 13 have speech subjectively described as always understandable; and nine of 13 have no significant restrictions in their diet. CONCLUSION: This treatment program is feasible and effective in patients with advanced oropharynx cancer and produces an excellent functional outcome in most long-term survivors. Modifications to optimize patient selection, minimize toxicity, and improve local control are indicated. The relative toxicity, efficacy, and functional outcome provided by this and other chemotherapy and RT programs versus either standard surgery and/or RT options can only be addressed in a randomized comparison of these therapies.

Adult↗

Brachytherapy in sarcomas.

Historically, amputation was the standard local treatment for soft tissue sarcomas of the extremity. Although this procedure provided excellent local control, the adverse impact of this procedure on quality of life was obvious. In an effort to maximize the functional outcome of sarcoma therapy, various groups initiated studies aimed at doing less radical operations in conjunction with radiation therapy.

Actuarial Analysis↗

High-dose-rate intraoperative radiation therapy for colorectal cancer.

Last month, the authors presented the principles of high-dose-rate intraoperative radiation therapy (HDR-IORT), a new approach to intraoperative radiation delivery, as well as their criteria for patient selection, the goals of surgery, and their approach to minimizing surgical morbidity. This month, the authors present the technical aspects of delivering HDR intraoperative brachytherapy, their dosimetry atlas, and their results using HDR-IORT in the treatment of patients with colorectal cancer.

Adenocarcinoma↗

High-dose-rate intraoperative radiation therapy for colorectal cancer.

Intraoperative radiation therapy (IORT) has the obvious advantage of maximally irradiating the tumor bed while eliminating surrounding normal organs from the field of radiation. This approach has been especially useful when the required radiation dose exceeds the tolerance dose of the surrounding normal tissues. However, the application of IORT has been significantly limited by cost, logistic issues, and technical problems related to delivering treatment to difficult anatomic areas. We have developed a new approach to IORT that obviates the need for patient transport: In a dedicated, shielded operating room, the surgery is performed and IORT is delivered via HDR remote afterloading. We have found this approach to be cost effective, logistically sound, and suitable for a wide range of anatomic sites. The technical aspects of the procedure, as well our preliminary results in colorectal cancer, will be presented.

Colorectal Neoplasms↗

Performance status after treatment for squamous cell cancer of the base of tongue--a comparison of primary radiation therapy versus primary surgery.

PURPOSE: To compare the quality of life and functional outcome in patients with squamous cell cancer of the base of tongue treated with primary radiation vs. primary surgery. METHODS AND MATERIALS: At our institution, patients with base of tongue cancer are primarily treated either by radiation or surgery depending upon the philosophy of their primary physician. Primary radiation consists of 45-54 Gy external beam radiation followed by an 192Ir implant delivering an additional 20-30 Gy over 2-3 days. A neck dissection is done at the same time as the implant for those with involved nodes. Primary surgery consists of resection of the base of tongue lesion, neck dissection and postoperative radiation therapy. Because both groups have similar local control in our experience (80-90%), we used a subjective performance status scale for head and neck cancer patients to assess the quality of life in these patients (0-100, 0 = worst function, 100 = normal function). This scale measures ability to eat in public, understandability of speech, and normalcy of diet. There were 30 radiation patients (21: T1-T2; nine: T3-T4) and ten surgery patients (five: T1-T2; five: T3-T4) available for long-term quality of life assessment. RESULTS: Patients treated with radiation had consistently better performance status scores and quality of life according to our study. This was true for those with early (T1-2) as well as more advanced (T3-4) disease. For eating in public, T1-2 patients had scores of 85 vs. 75 (p = .31) and T3-4 patients had scores of 82 vs. 35 (p < .0001) for radiation vs. surgery, respectively. For understandability of speech, T1-2 patients had scores of 92 vs. 65 (p = .0021), and T3-4 patients had scores of 95 vs. 35 (p < .0001) for radiation vs. surgery, respectively. For normalcy of diet, T1-2 patients had scores of 74 vs. 50 (p = .047), and T3-4 patients had scores of 78 vs. 32 (p = .0012) for radiation vs. surgery, respectively. In addition, we compared scores for early vs. advanced disease treated by the same modality. For radiation, there was no difference in all three functional categories for T1-2 vs. T3-4 (p = .84), showing that quality of life scores remain high for all stages. For surgery, functional status deteriorated significantly when comparing T1-2 vs. T3-4 (p = .0014), consistent with the fact that larger tumors require more extensive operations. CONCLUSION: Radiation therapy provides a better performance status than surgery for base of tongue cancer. This is true for both early and advanced disease. Because radiation also provides similar local control and survival, our data suggests that radiation may be the preferred strategy. Functional scores remain high for all T stages treated with radiation, but deteriorate with more advanced T stages for patients treated with surgery. Similar studies using objective criteria are needed to further compare these treatments.

Adult↗

Prognostic factors for recurrence and survival in head and neck soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas of the head and neck represent uncommon malignant neoplasms. With the exception of orbital and parameningeal sites, the treatment of sarcomas in the head and neck has not been standardized. The authors used a prospectively collected database of adult soft tissue sarcomas to identify prognostic factors for local control and survival. METHODS: A prospectively collected database of adult soft tissue sarcoma from 1982 to 1989 was analyzed for the impact of prognostic factors on local control and survival. Factors examined included histologic type, tumor grade, size, and resection margins. RESULTS: The overall and disease free survival at 5 years was 71 and 60%, respectively. Local control was 70% at 5 years. On univariate analysis, grade and margin status were predictors for local control. Analysis based on the Cox proportional hazard model revealed that margin status was the only significant factor in predicting local control. Grade and margin status were significant prognostic indicators for survival both on univariate analysis and in the Cox proportional hazard model. CONCLUSION: Patients with head and neck sarcomas should undergo wide excision with the removal of all gross disease and the acquisition of negative, microscopic surgical margins. Patients with positive margins should receive adjuvant radiotherapy for local control. High grade lesions place patients at risk for local recurrence and distant dissemination. Investigational regimens designed to prevent metastatic disease should be performed.

Adolescent↗

Treatment of liver metastases from colorectal cancer with radioactive implants.

BACKGROUND: Long-term survival and possible cure can be achieved in selected patients after resection of liver metastases from a colorectal primary tumor. In this study, the authors used radioactive implants as adjunctive therapy for patients who had incomplete resections of liver metastases. METHODS: From 1979 to 1990, 17 implants were performed in 12 patients (median age, 61 years). Brachytherapy was performed for microscopically positive margins in 7 implants and for gross residual disease in 10 implants. Volume implants were performed for gross residual disease using 125I seeds, with a median matched peripheral dose of 160 Gy. Most of the implants for microscopic residual disease were planar implants with 125I suture seeds, with a median treatment dose of 150 Gy. RESULTS: There were no serious postoperative complications. Overall median survival was 18 months, and 42% of patients survived 2 years or more. Extrahepatic metastases occurred in 83% of patients (10 of 12). Intrahepatic failure close to the implanted site occurred in 42% of patients (5 of 12), and intrahepatic failure anatomically remote from the implant site occurred in 25% (3 of 12). CONCLUSIONS: This approach is feasible and achieves reasonable local control of residual disease after resection of hepatic metastases from colorectal cancer. The anatomic pattern of failure supports efforts to intensify local therapy and to address the high rate of distant metastases.

Adult↗

Preoperative and postoperative adjuvant combination chemotherapy for adults with high grade soft tissue sarcoma.

BACKGROUND: Patients with high grade soft tissue sarcoma greater than or equal to 10 cm have a 3-year disease-free survival of approximately 30%. There is no convincing evidence, however, that postoperative adjuvant chemotherapy is beneficial. Preoperative chemotherapy has theoretical advantages over postoperative chemotherapy. METHODS: Twenty-nine evaluable patients with primary or recurrent high grade, nonmetastatic, soft tissue sarcoma were treated with two preoperative cycles of cyclophosphamide 500 mg/m2, doxorubicin 60 mg/m2, and DTIC 1000 mg/m2 before definitive surgery and radiation. Clinical and radiologic assessment of response to chemotherapy was performed preoperatively, and the resected specimen was examined for treatment effects. Patients who did not progress during preoperative therapy were eligible to receive four additional cycles of chemotherapy. Disease-free and overall survival rates of study patients were compared with two cohorts of historic controls. RESULTS: Although subjective changes in the firmness of some tumors were observed, only one patient met the criteria for partial response (3%, 2-sided 95% confidence interval = < 1-17%). Intratumoral hemorrhage, cystic necrosis, and liquefaction were observed regularly, and three tumors were more than 90% necrotic. Toxicity of the chemotherapy was acceptable, but patients were reluctant to receive postoperative therapy. The median time free from distant metastasis was 28 months; median survival was 35 months. These results were not superior to the experience with no chemotherapy, or with postoperative doxorubicin. CONCLUSIONS: Adjuvant chemotherapy for patients with soft tissue sarcoma remains investigational. There is a strong rationale, however, for continued investigation of preoperative chemotherapy for high risk patients using doxorubicin and ifosfamide with colony stimulating factor support. Development of sensitive and specific methods to assess response to preoperative chemotherapy is needed.

Adult↗

Use of decision analysis in planning a management strategy for the stage N0 neck.

OBJECTIVE: There are three major strategies in the treatment of patients with a stage N0 neck with squamous cell cancer of the head and neck: elective neck dissection, elective neck irradiation, and observation. Each has appropriate salvage strategies in the event of local recurrence. We used decision analysis to determine the optimal strategy for neck treatment as a function of the probability of occult cervical metastasis. DATA SOURCES: We used the bibliographies of current articles and books to access clinical studies of patients with stage N0 neck cancer. STUDY SELECTION: Studies that included large numbers of patients and contained a minimum 2-year follow-up, with results analyzed in terms of outcome as a function of stage of neck disease, were included. DATA EXTRACTION: Specific data points were extracted from the studies independently by multiple observers, and mean values were used in the decision analysis. DATA SYNTHESIS: A decision tree was constructed with use of a computer model to compare the three management strategies. Probabilities of each of the possible events depicted in the trees were inserted into the tree structure. These probabilities were gleaned from the literature as described above. A sensitivity analysis was performed to determine the optimal threshold for treatment of the neck. CONCLUSION: A patient with primary squamous cell carcinoma of the head and neck and stage N0 neck status should be observed if the probability of occult cervical metastasis is less than 20%. If the probability is greater than 20%, treatment of the neck is warranted. The treatment plan should ideally involve a single modality of therapy; both neck dissection and radiation therapy are quite efficacious in the clinical context, and the decision of which one to employ should be driven by the treatment of the primary lesion. Decision analysis is useful in complex clinical situations.

Carcinoma, Squamous Cell↗

Influence of surgical resection and brachytherapy in the management of superior sulcus tumor.

We analyzed the results of surgical treatment of all patients presenting with untreated superior sulcus tumors between 1974 to 1991 inclusive at our institution. Most patients received preoperative radiotherapy. We attempted to analyze the influence of surgical resection and intraoperative brachytherapy in obtaining locoregional control and disease-free survival. One hundred twenty-four patients underwent thoracotomy and 100 patients underwent resection. The overall 5-year survival rate was 26% for all patients and 30% for resected patients. Those patients receiving a complete resection achieved a 41% 5-year survival. The best single group were those patients undergoing a lobectomy (versus wedge resection) and en-bloc chest wall resection (60% 5-year survival). We were unable to demonstrate an advantage for the use of intraoperative brachytherapy in those patients with complete resection. For those patients with incomplete resection, the use of brachytherapy combined with preoperative or postoperative external radiation therapy resulted in a 9% 5-year survival. Locoregional failure was significant both in patients with complete resection and in patients with incomplete resection. Adverse prognostic factors included Horner's syndrome, N2 and N3 disease, T4 disease, and incomplete resections. In superior sulcus tumors, every attempt to completely resect the tumor by en-bloc chest wall resection combined with lobectomy and adequate nodal staging remains the surgical treatment of choice together with either preoperative, postoperative, or "sandwich" external radiation therapy.

Adult↗

Management of unresectable malignant tumors at the skull base using concomitant chemotherapy and radiotherapy with accelerated fractionation.

Between January 1988 and June 1992, 20 patients with unresectable malignant tumors at the skull base were treated. Eleven had T4 lesions of the paranasal sinus/cavity complex, and 9 had T4 nasopharynx cancer. All patients had stage IV disease by the American Joint Committee on Staging Criteria. The histology was squamous cell cancer in 15 patients and other minor salivary gland histologies in 5. There was brain and/or dural invasion in 11 patients and orbital invasion in 9. All patients received radiation therapy with accelerated fractionation to a total of 70 Gy in 6 weeks. Concomitant cisplatin (100 mg/m(2)) was given on days 1 and 22 of radiation. Seven patients received mitomycin C (7.5 mg/m(2)) on days 1 and 22, plus adjuvant chemotherapy with cisplatin and vinblastine. Median follow-up was 11 (range: 1 to 43) months. At 2 years, local progression-free survival was 94%, distant metastases-free survival was 57%, and overall survival was 80%. Complications occurred in 20% and caused the death of 1 patient. Treatment of this group of patients with aggressive chemotherapy and radiation therapy produced excellent local control in our early experience, but longer follow-up is needed. There is a high rate of distant failure. Future strategies are outlined.

Journal Article↗

Larynx preservation with combined chemotherapy and radiation therapy in advanced hypopharynx cancer.

Twenty-five untreated patients with advanced, resectable squamous cell carcinoma of the hypopharynx, for whom standard treatment would have required total laryngectomy, were treated with one to three cycles of cisplatin-based chemotherapy with larynx preservation as the goal. Patients with a major (complete or partial) response to chemotherapy at the primary site were treated with definitive radiation therapy, with total laryngectomy reserved for salvage; patients with less than a partial response to chemotherapy had total laryngectomy and postoperative radiation therapy recommended. Four patients had a poor response to chemotherapy and thus were not candidates for laryngectomy. Total laryngectomy was required for initial induction chemotherapy failure in five patients and for local recurrence in five others. Three additional patients had unresectable recurrence. Successful larynx preservation was achieved in 32% (8 of 25). With a median follow-up period of 41 months, the actuarial overall and failure-free 2-year survival rates were 44% and 32%, respectively. These preliminary data suggest larynx preservation is feasible in patients with advanced lesions of the hypopharynx. Improved local and regional control must be incorporated into the larynx preservation approach for hypopharyngeal lesions. A prospective, randomized study is necessary for a more valid comparison with conventional therapy, including comparative assessments of survival, morbidity, cost and functional results.

Adult↗

A prospective randomized trial of adjuvant brachytherapy in the management of low-grade soft tissue sarcomas of the extremity and superficial trunk.

PURPOSE: This study was designed to evaluate the impact of adjuvant brachytherapy (BRT) on local and systemic recurrence rates in patients with low-grade sarcoma. PATIENTS AND METHODS: Forty-five patients with histologic low-grade, completely resected soft tissue sarcomas of the extremity or superficial trunk were entered onto this trial. Following resection of all gross disease, patients were randomized to the BRT arm (n = 22) or to the no-BRT arm (n = 23). On the fifth or sixth postoperative day, catheters were loaded with iridium 192 to deliver a dose of 45 Gy to the tumor bed over 4 to 6 days. RESULTS: The two groups were evenly distributed with respect to the distribution of presentation status (primary v recurrent), tumor site (trunk v extremity, proximal v distal extremity), tumor size (< 5 cm v > or = 5 cm), tumor depth (superficial v deep), and microscopic tumor margins (positive v negative). The predominant histopathologic diagnosis in each group was liposarcoma (BRT, 13 of 22 [59%]; no BRT, 14 of 23 [61%]) with other histopathologic subtypes evenly distributed between the two groups. The median follow-up duration among the ongoing survivors is 67 months. One patient in the BRT group developed systemic disease and died of progressive disease. Local recurrence occurred in five of 23 patients (22%) in the no-BRT group and six of 22 patients (27%) in the BRT group (P = .60). CONCLUSION: Adjuvant radiation in the form of BRT does not appear to decrease local recurrence rates following complete resection of low-grade extremity and superficial trunk soft tissue sarcomas. Other adjuvant approaches, such as external-beam radiotherapy, are required to have a significant impact on local recurrence rates in this group of patients.

Brachytherapy↗

Consensus guidelines for high dose rate remote brachytherapy in cervical, endometrial, and endobronchial tumors. Clinical Research Committee, American Endocurietherapy Society.

PURPOSE: A large number of medical centers have recently instituted the use of High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in treatment regimens, techniques, and dosimetry being used and there are no national standard protocols or guidelines for optimal therapy. METHODS AND MATERIALS: The Clinical Research Committee (CRC) of the American Endocurietherapy Society (AES) met to formulate consensus guidelines for HDRAB in cervical, endometrial, and endobronchial tumors. CONCLUSION: Each center is encouraged to follow a consistent treatment policy in a controlled fashion with complete documentation of treatment parameters and outcome including efficacy and morbidity. Until further clinical data becomes available, the linear quadratic model can be used as a guideline to formulate a new HDR regimen exercising caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The treatments should be fractionated as much as practical to minimize long term morbidity. As more clinical data becomes available, the guidelines will mature and be updated by the Clinical Research Committee of the AES.

Brachytherapy↗

Long-term results of a prospective randomized trial of adjuvant brachytherapy in the management of completely resected soft tissue sarcomas of the extremity and superficial trunk.

PURPOSE: A prospective randomized trial evaluating adjuvant brachytherapy for soft tissue sarcomas was conducted between July 1982 and July 1987. METHODS AND MATERIALS: One hundred twenty-six patients with soft tissue sarcoma of the extremity or superficial trunk (STS) underwent grossly complete resection with limb-sparing surgery. Intra-operatively, patients were randomized to receive either adjuvant brachytherapy (BRT) or no further therapy (no BRT). BRT consisted of an Iridium-192 implant which delivered 4200-4500 cGy over 4-6 days. Total hospital stay for combined surgery and BRT was 10-14 days. Patients in each group were well matched with respect to age, sex, site, tumor size, depth, histologic type, and grade. Median follow-up is 66.5 months for all living patients. RESULTS: At 5 years, local control was 82% in the BRT group vs. 67% in the no BRT group (p = .049). When analyzed by histologic grade, high grade tumors had local control of 90% with BRT vs. 65% with no BRT (p = .013). There was no difference in local control in the low grade patients in either arm. At 5 years, the proportion free of distant metastases was approximately 76% in both arms, with no difference between BRT and no BRT. When analyzed by grade, high grade patients had a similar proportion free of distant metastasis in the BRT vs. no BRT arms despite improved local control in those receiving BRT. Similarly, the disease-specific survival for all patients at 5 years was 81% for BRT vs. 80% for no BRT (p = NS). When analyzed by grade, and treatment (BRT vs. no BRT), 5-year disease-specific survival for high grade was the same in both groups. CONCLUSIONS: Adjuvant BRT significantly improves local control in completely resected STS. This improvement is confined to patients with high grade histology. BRT provides excellent local control in this group, and significantly shortens the treatment time when compared to adjuvant external beam radiation. However, the improved local control does not translate into either decreased distant metastasis or increased disease-specific survival.

Age Factors↗

A nomograph for permanent implants of palladium-103 seeds.

103Pd is being substituted for 125I in permanent implants for which it is desired to deliver a higher initial dose rate while maintaining readily achieved radiation protection. We have constructed a nomograph to assist in determining both the total seed strength required and the appropriate needle spacing for 103Pd implants. We have calculated the "matched peripheral dose" (MPD), that is, the dose for which the isodose contour volume is equal to the target volume, for 64 125I and 13 103Pd actual implants as if 103Pd had been used for all of them, employing a computer lookup table based on single-seed dose distribution measurements in solid water. The calculated data were used to obtain a least-squares fit to a linear relationship between the logarithm of the total seed strength for a given MPD and the logarithm of the average dimension, da (cm). We found that, for a nominal MPD of 11,500 cGy, total seed strength (in mCi) is given by 3.2 da2.56. A 103Pd nomograph has been constructed on the basis of this power function relationship. Our nomographic guide for planning 103Pd implants calls for total seed strength to increase significantly faster as a function of target volume average dimension than is the case for 125I. This nomograph will facilitate the application of 103Pd seeds in permanent implants.

Brachytherapy↗

Postoperative radiation therapy for squamous cell carcinomas of the oral cavity and oropharynx: impact of therapy on patients with positive surgical margins.

PURPOSE: The presence of a positive or close margin after resection of a squamous cancer of the head and neck is associated with a significant risk of local recurrence. To determine the efficacy of postoperative radiation therapy for patients with advanced oral cavity and oropharyngeal cancers with inadequate margins of resection, the present retrospective analysis was undertaken. METHODS AND MATERIALS: One hundred and two patients were treated with surgery and postoperative radiation therapy for advanced squamous cell carcinomas of the oral cavity and oropharynx. The anatomic subsites treated include oral tongue (n = 29), floor of mouth (n = 22), base of tongue (n = 31) and tonsillar fossa (n = 20). Twenty-five patients (25%) had positive margins, 41 patients (40%) had close margins (< or = 0.5 cm from the surgical margin) and 36 (35%) had negative margins. The median radiation dose was 6000 cGy. RESULTS: With a median follow-up of 7 years, the actuarial control rate for patients with positive, close and negative margins was 79%, 71%, and 79%, respectively. When postoperative doses of > or = 60 Gy were delivered to patients with positive/close margins (excluding patients with oral tongue lesions), the 7-year actuarial control was 92%. In similar patients receiving < 60 Gy, the actuarial control was 44% (p = 0.0007). Compared to other anatomic subsites, inferior control rates were obtained with oral tongue lesions. For this subsite, the control rates for positive, close, and negative margins were 50%, 62% and 69% respectively. CONCLUSION: We conclude that excellent local control can be achieved with postoperative radiation therapy, despite the presence of inadequate margins of resection, when doses of > or = 60 Gy are used. Future strategies must be directed at further improving these results in patients with oral tongue lesions.

Carcinoma, Squamous Cell↗