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Biomedical subjects

L R Prosnitz

Publications and source records attributed to L R Prosnitz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Impact of consolidation radiotherapy in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow rescue.

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Adult↗
PubMed1999

Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis.

PURPOSE: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. METHODS: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. RESULTS: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL CONCLUSION: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients.

Adult↗
PubMed1999

Mounting evidence for postmastectomy locoregional radiation therapy.

Postmastectomy locoregional radiation therapy markedly reduces the risk of locoregional recurrence. Several randomized trials, including two recently updated studies with 10- to 15-year follow-up, demonstrate an improvement in overall survival with radiation therapy. This improvement is seen in patients with one to three positive axillary lymph nodes, as well those with four positive nodes. Therefore, postmastectomy radiation therapy should be considered in all patients with node-positive breast cancer. Computed tomography (CT)-based treatment planning is recommended to minimize the cardiopulmonary morbidity of radiation therapy.

Antineoplastic Agents↗
PubMed1998

Complications of axillary lymph node dissection for carcinoma of the breast: a report based on a patient survey.

BACKGROUND: Axillary lymph node dissection is commonly performed as part of the primary management of breast carcinoma. Its value in patient management, however, has recently been questioned. Few studies exist that document long term complications. METHODS: Four hundred thirty-two patients with Stage I or II breast carcinoma who were free of recurrence 2-5 years after surgery were identified. A cross-sectional survey was conducted to determine the prevalence of long term symptoms and complications as perceived by the patient, and patient and treatment factors that may have predicted complications were determined. Three hundred thirty of the 432 (76%) completed a mailed, self-administered questionnaire. In addition, the medical records of the 330 patients were reviewed. Patient and treatment factors were analyzed with logistic regression. RESULTS: Numbness was reported by 35% of patients at the time of the survey. Pain was noted in 30%, arm swelling in 15%, and limitation of arm movement in 8%. Eight percent reported episodes of infection or inflammation at some point since the diagnosis of breast carcinoma. The majority of symptoms were mild and interfered minimally with daily activities. Younger age (P=0.001) was associated with more frequent reporting of pain. Numbness was more common in younger patients (P=0.004) as well as in those with a history of smoking (P=0.012). There was a positive association of limitation of arm motion with adjuvant tamoxifen therapy (P=0.016). Arm swelling was associated with both younger age (P=0.004) and greater body surface area (P=0.008). Radiation therapy was associated with a higher frequency of infection or inflammation in the arm and/or breast (P=0.001). CONCLUSIONS: Mild symptoms, especially pain and numbness, are common 2-5 years after axillary lymph node dissection. The frequency of inflammation or infection in patients treated with radiation to the breast or chest wall after an axillary lymph node dissection may be greater than previously appreciated. Severe complications or symptoms that have a major impact on daily activities are uncommon. These findings should help health care providers and their patients with breast carcinoma weigh the pros and cons of axillary lymph node dissection.

Activities of Daily Living↗
PubMed1998

Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer.

BACKGROUND: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS: Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS: Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS: Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

Aged↗
PubMed1998

T classification and clivus margin as risk factors for determining locoregional control by radiotherapy of nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to determine risk factors that affect locoregional control of nasopharyngeal carcinoma (NPC) after radiotherapy. Computed tomography (CT) is utilized for radiotherapy planning and for identifying high risk anatomic areas. METHODS: Between April 1990 and December 1993, 40 consecutive patients (1 in Stage I, 3 in Stage II, 5 in Stage III, and 31 in Stage IV) who had locoregional NPC were given definitive radiotherapy at the Koo Foundation Sun Yat-Sen Cancer Center in Taipei, Taiwan. All patients had individualized CT treatment planning. The dimension of each tumor as shown on the treatment planning CT were mapped on conventional simulation films. The extent of each tumor was further affirmed by magnetic resonance imaging (MRI) and the tumor map revised as necessary. The primary radiation fields were designed to include the primary tumor and potential spread areas with appropriate margins. Concurrent chemotherapy was also given to 35 patients (87.5%) who had positive cervical lymph nodes or primary tumors extending beyond the nasopharynx. RESULTS: By the end of December 1995, after a median follow-up of 42 months and minimal follow-up of 24 months, the locoregional control rate at 4 years was 84.8% (95% confidence interval [CI], 72.3-97.3), disease free survival 68.4% (95% CI, 52. 1-84.7), and overall survival 76.7% (95% CI, 63.4-90.0). The radiation field margin near the sphenoid sinus averaged 1.9 cm, the clivus margin 1.1 cm, the pterygoid fossa margin 2.0 cm, and the oral cavity margin 1.7 cm. Risk factor analysis revealed that T classification and the radiation field margin at the clivus were the most important factors for locoregional control of the tumor. The locoregional control rates were 92.6% (25/27) for T1-T3 patients and 76.9% (10/13) for T4 patients (P = 0.03). The locoregional control rates were 71.4% (5/7) for patients with a clivus margin < 1 cm and 90.6% (29/32) for patients with a clivus margin > or = 1 cm (P = 0.08). CONCLUSIONS: The excellent locoregional control observed in this series may be attributed to the concurrent chemotherapy and radiotherapy as well as meticulous treatment planning with CT and MRI. The precise delineation of the involved area with the aid of CT, which is taken while the patient is in the position for irradiation, serves to define the necessary safety margin of the radiation field. T classification and clivus margin are the most important factors in determining locoregional control of radiotherapy of NPC. The statistical trend observed in this study indicated that the clivus margin should be adequate to reduce the failure around the clivus, as all local recurrences were observed in this area.

Adult↗
PubMed1998

Radiotherapy alone for medically inoperable stage I non-small-cell lung cancer: the Duke experience.

PURPOSE: To review our experience treating clinical Stage I non-small-cell lung carcinoma with radiotherapy alone using modern techniques and staging. The effect of dose and volume on outcome is to be analyzed. METHODS: Between January 1980 and December 1995, 156 patients with Stage I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administration Medical Center. Fifteen patients were excluded from analysis (7 treated with palliative intent, and 8 lost to follow-up immediately following radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenocarcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; presenting symptoms: weight loss 26%, cough 23%, none (incidental diagnosis) 57%. All patients underwent simulation prior to radiotherapy using linear accelerators of > or = 4 MV. No patients received surgery or chemotherapy as part of their initial treatment. The median dose of radiotherapy (not reflecting lung inhomogeneity corrections) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractionation. The majority of cases included some prophylactic nodal regions (73%). RESULTS: Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- and 5-year overall survival was 39% and 13%, respectively (median 18 months). The corresponding cause-specific survival was 60%, and 32% (median 30 months). On multivariate analysis, significant factors influencing overall and/or cause-specific survival were age, squamous cell histology, incidental diagnosis, and pack-years of smoking. There was a nonsignificant trend towards improved cause-specific survival with higher radiotherapy doses and larger treatment volumes. On patterns of failure analysis, 42% of failures were local-only and 38% were distant-only. Regional-only failure occurred in 4 patients (7%), 3 of whom failed solely in an unirradiated nodal site. Analysis of factors correlating with local failure at 2 years was performed using a multinominal logistic regression analysis. Significant factors associated with a lower local failure included incidental diagnosis and absence of cough with a strong trend toward significance for higher radiotherapy dose (p = 0.07) and larger treatment volume (p = 0.08). Patients who were locally controlled had an improved cause-specific survival at 5 years over those who were not controlled (46% vs. 12%, p = 0.03). Grade III-V complications occurred in 2 patients (1.5%). CONCLUSION: Patients with clinical Stage I medically inoperable non-small-cell lung cancer treated with contemporary radiotherapy alone achieved a 5-year cause-specific survival of 32%. Uncontrolled lung cancer was the primary cause of death in these patients, and local failure alone represented the most common mode of failure (42%). Patients who were locally controlled had a significantly improved cause-specific survival over those who failed locally. Because higher doses of radiotherapy appear to provide improved local control, studies of dose escalation are warranted until dose-limiting toxicity is observed.

Adenocarcinoma↗
PubMed1997

Radiation techniques for the treatment of Hodgkin's disease with combined modality therapy or radiation alone.

This article reviews radiation techniques including field arrangements, anatomic borders, and doses for the treatment of Hodgkin's disease when radiotherapy is being used as the sole treatment and when it is part of a planned combined modality program with chemotherapy. We describe the techniques currently in use at Duke University Medical Center. Particular emphasis is placed on the evidence regarding the appropriate extent of the treatment field and the doses of radiation necessary to achieve local control. These issues assume increasing importance as we attempt to maintain high cure rates for Hodgkin's disease but lower the frequency of serious long-term complications.

Adult↗
PubMed1997

Comparison of two repositioning devices used during radiation therapy for Hodgkin's disease.

PURPOSE: Patients irradiated for Hodgkin's disease are fixed in an immobilization cradle to improve repositioning. In the early 1990s, we changed our cradle system from a "short" upper torso cradle to an extended near-total body cradle that also includes the lower torso and thighs. In this study, we assess the impact of the extended cradle on the reproducibility of patient repositioning during irradiation of Hodgkin's disease. METHODS AND MATERIALS: A total of 782 port films of 56 patients treated immediately before and after the change-over were studied to assess positioning reproducibility. Patients treated prior to 1993 were positioned in the short cradle, while those treated 1993 and later were positioned in the extended cradle. All treatment were delivered via anterior and posterior fields and treatment areas above and below the diaphragm were considered separately and together. All treatment fields were simulated and the field shape was designed on anterior and posterior radiographs. Discrepancies in field placement between the simulation radiographs and subsequent port films were noted by a radiation oncologist and requests for position adjustment (both translational and rotational shifts) were noted. The number, magnitude, and direction of any physician-requested position adjustment on port films were retrospectively reviewed. For the purpose of scoring the frequency of field misplacements, when an adjustment was noted on two port films taken during the same treatment session (i.e., a left shift on both an anterior and a posterior port film), it was scored as only one event. A two-tailed chi-square test was used to compare the differences in requested shifts in the two patient groups. RESULTS: The study population consisted of 56 patients (31 short and 25 extended cradle) representing 92 treatment sites. A total of 782 port films representing 450 treatment setups were analyzed (292 above and 158 below the diaphragm). When all port films above the diaphragm (mostly mantle fields) are considered, position adjustments were requested in 13.4% (21 out of 157) of treatment setups with the upper torso cradle and in 5.9% (8 out of 135) of treatment setups with the extended cradle (p = 0.054). When all port films below the diaphragm (mostly paraaortic/spleen and pelvic fields) are considered, position adjustments were requested in 33.8% (27 out of 80) of treatment setups with the upper torso cradle and in 16.7 % (13 out of 78) of treatment setups with the extended cradle (p = 0.056). A reduction in the frequency of both translational and rotational adjustments were seen. When both treatment sites are combined, position adjustments were requested in 20.3% (48 out of 237) of treatment setups with the upper torso cradle and in 9.9% (21 out of 213) of treatment setups when the extended cradle was used (p = 0.0086). CONCLUSIONS: The extended cradle provides superior repositioning of patients undergoing radiation therapy for Hodgkin's disease. Differences observed in setup accuracy in this study underscore the importance of aggressive immobilization of patients with Hodgkin's disease. Increased accuracy of daily setup may provide an opportunity to improve the therapeutic ratio both by increased likelihood of tumor control and decreased risk of normal tissue complications.

Equipment Design↗
PubMed1997

Quantification of radiation-induced regional lung injury with perfusion imaging.

PURPOSE: To better understand the dose and time dependence of radiation therapy (RT)-induced regional lung dysfunction as assessed by changes in regional lung perfusion. METHODS AND MATERIALS: Patients who were to receive RT for tumors in and around the thorax, wherein portions of healthy lung would be incidentally irradiated, were prospectively studied. Regional function was assessed pre- and post-RT with single photon emission computed tomography (SPECT) lung perfusion scans, obtained following the intravenous administration of approximately 4 mCi of technetium-99m macroaggregated albumin. Pre-RT computed tomography (CT) scans were used to calculate the three-dimensional (3D) dose distribution, reflecting tissue density inhomogeneity corrections. Each SPECT scan was correlated with the pre-RT CT scan, and the 3D dose distribution. Changes in regional lung perfusion were correlated with regional RT dose, at various time intervals following radiation. RESULTS: The data from 20 patients (7 breast cancer, 5 lymphoma, 1 esophagus, 1 sarcoma, and 6 lung cancer) have been analyzed. Patients with gross intrathoracic lung cancers causing obstruction of regional pulmonary arteries were not included. For most patients, there is a statistically significant dose-dependent reduction in regional blood flow at all time points following radiation. While a time dependence is suggested in the high dose range, the limited amount of data prevents meaningful statistical evaluation. CONCLUSIONS: Radiation therapy-induced regional lung dysfunction occurs in a dose-dependent manner and develops within 3-6 months following radiation. In contrast to classical "sigmoid" dose-response curves, described mainly for changes following whole lung irradiation, these data suggest a more gradual relationship between regional dysfunction and RT dose. Retraction of irradiated lung with secondary movement of unirradiated lung into the "3D-defined irradiated volume" may have introduced inaccuracies into this analysis. Additional studies are currently underway to assess this possibility and better refine this dose-response curve. Studies are underway to determine if changes in assessments of whole lung function, such as pulmonary function tests, can be predicted by summing the regional changes observed.

Dose-Response Relationship, Radiation↗
PubMed1997

Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck.

PURPOSE: Tumor hypoxia adversely affects short term clinical radiation response of head and neck cancer lymph node metastases and long term disease-free survival (DFS) in cervix carcinoma. This study was performed to evaluate the relationship between tumor hypoxia and DFS in patients with squamous carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Pretreatment tumor pO2 was assessed polarographically in SCCHN patients. All patients were AJCC Stage IV and had pretreatment oxygen measurements taken from locally advanced primaries (T3 or T4) or neck nodes > or = 1.5 cm diameter. Treatment consisted of once daily (2 Gy/day to 66-70 Gy) or twice daily irradiation (1.25 Gy B.I.D. to 70-75 Gy) +/- planned neck dissection (for > or = N2A disease) according to institutional treatment protocols. RESULTS: Twenty-eight patients underwent tumor pO2 measurement. The average pre-treatment median pO2 was 11.2 mm Hg (range 0.4-60 mm Hg). The DFS at 12 months was 42%. The DFS was 78% for patients with median tumor pO2 > 10 mm Hg but only 22% for median pO2 < 10 mm Hg (p = 0.009). The average tumor median pO2 for relapsing patients was 4.1 mm Hg and 17.1 mm Hg in non-relapsing (NED) patients (p = 0.007). CONCLUSION: Tumor hypoxia adversely affected the prognosis of patients in this study. Understanding of the mechanistic relationship between hypoxia and treatment outcome will allow for the development of new and rational treatment programs in the future.

Carcinoma, Squamous Cell↗
PubMed1997

Combined external beam irradiation and external regional hyperthermia for locally advanced adenocarcinoma of the prostate.

PURPOSE: To determine the safety and efficacy of combined external beam irradiation and external regional hyperthermia in the treatment of adenocarcinoma of the prostate. METHODS AND MATERIALS: From 1987 to 1994, 30 patients received combined external beam irradiation and external regional hyperthermia for locally advanced prostate cancer. The results of the 21 patients with newly diagnosed (n = 18) or locally recurrent (n = 3) adenocarcinoma are reported herein. No patient had evidence of distant metastases. Total radiotherapy doses of 65-70 Gy to the prostate were planned using a four-field box technique. Hyperthermia treatments were delivered using an annular phased array microwave device. The treatment goal was to achieve temperatures > or = 42 degrees C in all measured points within the prostate. RESULTS: Of the newly diagnosed patients, 16 out of 18 (89%) had T3 or T4 tumors, 11 out of 18 (61%) had Gleason scores of 7-9, and the mean pretreatment Prostate Specific Antigen (PSA) was 69 ng/ml. The median follow-up of all 21 patients was 36 months. None of the patients achieved the treatment goal of all intratumoral temperatures > or = 42 degrees C. The mean CEM 43 T90 was 2.34 min. The disease-free survival at 36 months is 25%; 12 out of 18 (67%) of the patients have relapsed. The only significant predictor of relapse was pretreatment PSA. There were no complications > Grade 3. CONCLUSIONS: In spite of the inability to achieve high tumor temperatures, the relapse-free survival rate in this population of patients with very advanced localized prostate cancer treated with radiation therapy plus hyperthermia compares favorably with most series using radiation therapy alone. Further studies aimed at improving the ability to deliver hyperthermia to the prostate are warranted.

Adenocarcinoma↗
PubMed1997

"One to three" or "four or more"?: selecting patients for postmastectomy radiation therapy.

A review of randomized trials suggesting an improvement in overall patient survival with postmastectomy radiation therapy revealed that most patients in these studies had three or fewer positive axillary lymph nodes. Therefore, it is logical to consider using postmastectomy radiation therapy in all lymph node positive patients, not just those with four or more positive lymph nodes.

Breast Neoplasms↗
PubMed1997

The role of radiation therapy after local excision of invasive and noninvasive breast cancer.

Data from randomized and nonrandomized studies demonstrate that the addition of breast irradiation after local excision of invasive and noninvasive breast cancers markedly reduces the breast failure rate. Local excision with breast irradiation remains the standard approach for breast-conserving therapy for both invasive and noninvasive cancers. Some data suggest that there might be patient subgroups that could be treated with local excision without radiotherapy, but additional studies are necessary to better define these groups.

Antineoplastic Agents, Hormonal↗
PubMed1997

Lumpectomy with and without radiation for early-stage breast cancer and DCIS.

Breast-conserving therapy with lumpectomy and breast irradiation is an accepted standard treatment for patients with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). For both diseases, investigators have tried to identify subgroups of patients who can be "safely" treated with lumpectomy without radiation. Some data suggest that it may be reasonable to omit radiation therapy in patients with small, low-grade invasive or noninvasive tumors and/or in "elderly" patients. Additional studies are needed to better identify criteria to prospectively select appropriate patients for treatment with lumpectomy alone.

Aged↗