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Biomedical subjects

L B Marks

Publications and source records attributed to L B Marks.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1996

Histologically confirmed pineal tumors and other germ cell tumors of the brain.

BACKGROUND: This study examined the outcome of patients with histologically confirmed pineal region tumors. METHODS: One hundred thirty-five patients with histologically confirmed pineal tumors and other germ cell tumors of the brain were evaluated retrospectively. The pineal parenchymal tumors (PPTs) included 15 pineoblastomas (PB), 2 mixed PPTs, 4 PPTs with intermediate differentiation, and 9 pineocytomas. The germ cell tumors included 48 germinomas, 26 mixed germ cell tumors, 11 mature teratomas, 9 immature teratomas, 6 malignant teratomas, 2 yolk sac tumors, and 3 choriocarcinomas. Patients were treated with various combinations of chemotherapy, radiotherapy, and surgery. The duration of follow-up ranged from 0.25 to 37.3 years, with a median follow-up of 5.3 years. RESULTS: The 5-year patient survival rate was 86% for those with mature teratomas; 86% with pineocytomas; 80% with germinomas; 67% with immature teratomas; 49% with PPTs, excluding pineocytomas; 38% with mixed germ cell tumors; and 17% with other germ cell histologies (P = 0.0001). The delivery of > 44 Gray (Gy) to germinomas and > 50 Gy to PPTs and nongerminomatous germ cell tumors (NGGCTs) other than mature and immature teratomas was associated with improved survival. A greater extent of resection was associated with a higher rate of survival in all patients with NGGCTs. The administration of chemotherapy was associated with improved survival in those patients with NGGCTs other than mature and immature teratomas. CONCLUSIONS: Prognosis was dependent on tumor type. Obtaining a tissue diagnosis made it possible to tailor therapy according to tumor type and potentially improve the survival of patients. Survival was dependent on the dose of radiation administered to patients with PPTs, germinomas, and NGGCTs other than mature and immature teratomas. More extensive resection and the use of chemotherapy were also associated with improved survival in subgroups of patients with NGGCTs. Treatment recommendations are described in detail in the article.

Adolescent↗
PubMed1996

High-dose, hyperfractionated, accelerated radiotherapy using a concurrent boost for the treatment of nonsmall cell lung cancer: unusual toxicity and promising early results.

PURPOSE: The treatment of nonsmall cell lung cancer (NSCLC) with conventional radiotherapy (RT) results in inadequate local tumor control and survival. We report results of a Phase II trial designed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated, accelerated treatment schedule with a concurrent boost technique. METHODS AND MATERIALS: A total of 49 patients with unresectable Stage IIIA/IIIB (38 patients) or medically inoperable Stage I/II (11 patients) NSCLC were prospectively enrolled in this protocol. Radiation therapy was administered twice daily, 5 days/week with > 6 h between each treatment. The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each. Using a concurrent boost technique, electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy. RESULTS: Median survival for the entire group of 49 patients is 15.3 months. Actuarial survival at 2 years is 46%: 60% for 11 Stage I/II patients, 55% for 21 Stage IIIA patients, and 26% for 17 Stage IIIB patients. The actuarial rate of freedom from local progression at 2 years is 64% for the entire group of 49 patients: 62% for Stage I/II patients, 70% for Stage IIIA patients, and 55% for Stage IIIB patients. Patients who underwent serial bronchoscopic reevaluation (4 Stage I/II, 8 Stage IIIA, and 6 Stage IIIB) have an actuarial rate of local control of 71% at 2 years. The median total treatment time was 32 days. Nine of 49 patients (18%) experienced Grade III acute esophageal toxicity. The 2-year actuarial risk of Grade III or greater late toxicity is 30%. The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20% and 15%, respectively. CONCLUSION: This treatment regimen administers a substantially higher biologically effective dose compared with conventional and pure hyperfractionation treatment schedules. The overall rate of acute and late toxicity was acceptable. Preliminary rates of overall survival and local control and freedom from local progression compare favorably to results reported with pure hyperfractionated radiotherapy and chemoradiotherapy.

Aged↗
PubMed1996

Nongerminomatous germ cell tumors of the brain.

PURPOSE: This analysis was performed to determine the clinical outcome of patients with primary nongerminomatous germ cell tumors of the brain. The efficacy of various treatment options was evaluated. METHODS AND MATERIALS: A total of 57 patients with primary nongerminomatous germ cell tumors of the brain were identified. Patient-related data were collected and analyzed retrospectively. Follow-up in surviving patients ranged from 3 to 243 months (median follow-up 36). Survival and failure rates were determined using the Kaplan-Meier method, and differences between the survival curves were evaluated using either the log rank test or the Wilcoxon test. RESULTS: The 3-year survival rate was 86% for patients with mature teratomas, 67% for patients with immature teratomas, 44% for patients with mixed germ cell tumors, and 13% for patients with the other histologic types (p = 0.02). The 3-year survival rate was 0% for patients having biopsies alone, 32% for patients having subtotal resections, and 73% for patients having gross total resections (p = 0.0001). Patients with tumors other than mature or immature teratomas were evaluated for possible relationships between the administration of chemotherapy or radiotherapy and survival. Patients who received chemotherapy had a 3-year survival rate of 56% compared to 8% for those patients who did not receive chemotherapy (p = 0.0001) Patients who received radiotherapy had a 3-year survival rate of 46% compared to 11% for those patients who did not receive radiotherapy (p = 0.0015). CONCLUSION: The survival of patients with primary nongerminomatous germ cell tumors of the brain is dependent on tumor histology and the extent of surgical resection. Patients with tumors other than mature or immature teratomas appear to benefit from the administration of chemotherapy and radiotherapy.

Brain Neoplasms↗
PubMed1995

Conformal radiation therapy with fixed shaped coplanar or noncoplanar radiation beam bouquets: a possible alternative to radiosurgery.

PURPOSE: Three-dimensional (3D) geometric conformation of the therapeutic dose volume to the shape of a target tissue volume is the motivation for both conformal radiotherapy and radiosurgery. Although noncoplanar arcs have a clear physical and geometric advantage over fixed fields for small spherical targets, those advantages are reduced for large or irregularly shaped targets where static fields can be individually shaped. We have developed a system that allows efficient and flexible design and reliable delivery of customized "bouquets" of fixed nonopposed coplanar or noncoplanar shaped fields, resulting in highly uniform dose distributions. This report describes our initial experience using beam bouquets to treat intracranial lesions. METHODS AND MATERIALS: Patients with primary (11) or metastatic (4) intracranial lesions with a maximum diameter less than approximately 6 cm, most of whom candidates for single-fraction radiosurgery, were treated with beam bouquets of four to eight nonopposed coplanar or noncoplanar beams. Doses ranged from 16-20 Gy in four fractions for recurrent lesions (8) to 45 to 68 Gy in 25 to 34 fractions for primary lesions (7). The patients were immobilized with custom foam head supports and face masks attached to a fixed base plate. Planning computed tomography scans were acquired, from which the physician developed the custom beam bouquet using 3D treatment-planning tools. The bouquet was designed based primarily on geometric concerns. The bouquet was subsequently modified to add wedge filters chosen by vector analysis of dose gradients to achieve uniform dose over the volume of beam crossfire. At the time of treatment, the isocenter was placed using the instructions provided by the treatment-planning system and pretreatment orthogonal port films were compared to digitally reconstructed radiographs (DRR) to assure proper isocenter placement. For several situations, the 3D dose distributions resulting from alternative coplanar and noncoplanar plans were compared. RESULTS: Each patient was treated without incident. Daily pretreatment port films showed excellent reproducibility of isocenter placement in 87% of setups. With short follow-up (0-12 months), two patients with recurrent glioblastoma experienced clinical deterioration 2 to 4 weeks following treatment. One had increased edema on scans and responded to steroids. Six patients clinically improved following radiation therapy. Review of alternative treatment plans reveals that the relative utility of coplanar vs. noncoplanar beams is likely dependent on the location of the lesion. Noncoplanar beam bouquets are likely preferable to coplanar beams when the target is located in the central regions of the head. Coplanar beams are likely adequate, and possibly preferable, for peripherally located targets. CONCLUSION: The biological advantages of fractionation and the physical advantages of radiosurgery are exploited with this approach. The use of multiple nonopposed coplanar or noncoplanar conformal wedged fields provides a uniform dose to the target and acceptable dose gradient at the target edge. This technique may prove to be an alternative to arc-based radiosurgery in some settings and has the potential advantages that fractionation should improve the therapeutic ratio, and each beam can be individually shaped to conform to irregularly shaped targets. Additional studies are underway to improve this system and better define its utility.

Adult↗
PubMed1995

The role of three dimensional functional lung imaging in radiation treatment planning: the functional dose-volume histogram.

PURPOSE: During thoracic irradiation (XRT), treatment fields are usually designed to minimize the volume of nontumor-containing lung included. Generally, functional heterogeneities within the lung are not considered. The three dimensional (3D) functional information provided by single photon emission computed tomography (SPECT) lung perfusion scans might be useful in designing beams that minimize incidental irradiation of functioning lung tissue. We herein review the pretreatment SPECT scans in 86 patients (56 with lung cancer) to determine which are likely to benefit from this technology. METHODS AND MATERIALS: Prior to thoracic XRT, SPECT lung perfusion scans were obtained following the intravenous injection of approximately 4 mCi of 99mcTc-labeled macro-aggregated albumin. The presence of areas of decreased perfusion, their location relative to the tumor, and the potential clinical usefulness of their recognition, were scored. Patients were grouped and compared (two-tailed chi-square) based on clinical factors. Conventional dose-volume histograms (DVHs) (DVFHs) are calculated based on the dose distribution throughout the computed tomography (CT)-defined lung and SPECT-defined perfused lung, respectively. RESULTS: Among 56 lung cancer patients, decreases in perfusion were observed at the tumor, adjacent to the tumor, and separate from the tumor in 94%, 74%, and 42% of patients, respectively. Perfusion defects adjacent to the tumor were often large with centrally placed tumors. Hypoperfusion in regions separate from the tumor were statistically most common in patients with relatively poor pulmonary function and chronic obstructive pulmonary disease (COPD). Considering all SPECT defects adjacent to and separate from the tumor, corresponding CT abnormalities were seen in only approximately 50% and 20% of patients, respectively, and were generally not as impressive. Following XRT, hypoperfusion at and separate from the tumor persisted, while defects adjacent to the tumor improved in several patients. In four patients who achieved a complete response scored by CT with chemotherapy prior to XRT, persistent hypoperfusion was present at and adjacent to the tumor site in three. Among 30 patients with cancers not arising in the lung (14 breast, 12 lymphoma, 4 others), perfusion defects were seen in only 4 (2 adjacent and 2 apart). Recognition of decreases in perfusion mainly impacted on treatment planning for a few patients with poor pulmonary function and limited target volumes. DVFHs have been useful in beam selection for patients with marked perfusion heterogeneities. CONCLUSIONS: Lung perfusion scans provide functional information not provided by CT scans that can be useful in designing radiation treatment beams that minimize incidental irradiation of the function regions of the lung. This approach appears to be most helpful in patients with gross intrathoracic lung cancer, especially those with small targets and relatively poor pulmonary function. One limitation of this approach is that some of the defects adjacent to the tumor site reperfuse following treatment, indicating that these scans identify perfusion rather than potential perfusion. Three dimensional functional data can be used to generate DVFHs that may be more predictive of the physiological consequences of the radiation than conventional DVHs. Additional work is currently underway to test this hypothesis.

Forced Expiratory Volume↗
PubMed1995

The lack of impact of pelvic irradiation on small bowel mobility: implications for radiotherapy treatment planning.

PURPOSE: Small bowel contrast is frequently used during simulation for patients undergoing pelvic radiotherapy to assist in the design of blocks that exclude small bowel from the radiation field. In many instances, a large field is treated to 45 gray (Gy), followed by a field reduction to exclude the small bowel. This prospective study was designed to assess whether the position and mobility of the small bowel changed after the initial 45 Gy, thereby determining whether a special small bowel series done at initial simulation is applicable at the time of field reduction. METHODS AND MATERIALS: Twelve patients undergoing pelvic irradiation were given small bowel contrast for their initial simulation. Radiographs were taken with the bladder empty and the bladder full. The location of the small bowel and its displacement with bladder distention was measured. This entire procedure was repeated prior to field reduction (after 39.6-46.0 Gy). RESULTS: There was no demonstrable alteration in small bowel mobility after 39.6-46.0 Gy. The approximate position of the small bowel relative to bony landmarks was unchanged. CONCLUSION: The position and mobility of the small bowel appears not to be affected by 39.6-46.0 Gy of pelvic radiotherapy. Therefore, it is reasonable to design reduced pelvic fields to exclude the small bowel based on special small bowel series done at initial treatment simulation.

Adult↗
PubMed1995

A customized head and neck support system.

PURPOSE: To describe a customized head and neck immobilization system for patients receiving radiotherapy including a head support that conforms to the posterior contour of the head and neck. METHODS: The system includes a customized headrest to support the posterior head and neck. This is fixed to a thermoplastic face mask that molds to the anterior head/face contours. The shape of these customized head and neck supports were compared to "standard" supports. RESULTS: This system is comfortable for the patients and appears to be effective in reproducing the setup of the treatment. CONCLUSIONS: The variability in the size and shape of the customized posterior supports exceeded that of "standard" headrests. It is our clinical impression that the customized supports improve reproducibility and are now a standard part of our immobilization system. The quantitative analysis of the customized headrests and some commonly used "standard" headrests suggests that the customized supports are better able to address variabilities in patient shape.

Equipment Design↗
PubMed1995

Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems.

Toxicity of the respiratory system is a common side effect and complication of anticancer therapy that can result in significant morbidity. The range of respiratory compromise can extend from acute lethal events to degrees of chronic pulmonary decompensation, manifesting years after the initial cancer therapy. This review examines the anatomic-histologic background of the lung and the normal functional anatomic unit. The pathophysiology of radiation and chemotherapy induced lung injury is discussed as well as the associated clinical syndromes. Radiation tolerance doses and volumes are assessed in addition to chemotherapy tolerance and risk factors and radiation-chemotherapy interactions. There are a variety of measurable endpoints for detection and screening. Because of the wide range of available quantitative tests, it would seem that the measurement of impaired lung function is possible. The development of staging systems for acute and late toxicity is discussed and a new staging system for Late Effects in Normal Tissues (LENT) is proposed.

Clinical Protocols↗
PubMed1995

The effectiveness of immobilization during prostate irradiation.

PURPOSE: To evaluate the effect of a hemibody foam cradle on the reproducibility of patient setup during external beam radiation treatment of prostate cancer. METHODS AND MATERIALS: Between January 1992 and April 1993, 74 patients received external beam radiation treatment to the prostate +/- nodes, generally with a four-field box technique. Forty-four of the 74 patients had a custom-made hemibody foam cast used in an attempt to improve setup accuracy. A review of the routine weekly port films was performed following the completion of therapy to determine the reproducibility of patient setup in all 74 patients. The physician's request of an isocenter shift was used as an indicator of reproducibility. Neither the treating technologists nor the physicians knew at the time the films were taken that the port films would be reviewed for setup reproducibility at a later date. The results were compared between the patients treated with (44) and without (30) an immobilization device. RESULTS: In the 44 immobilized patients, 213 routine checks of the isocenter were performed during the 7-week course of radiation therapy. In 17.4% of these instances (37 out of 213), an isocenter shift was requested. This rate is compared to 23.1% (30 out of 130) in the 30 patients who did not have the immobilization device (p < 0.2). There was a statistically significant reduction in isocenter shifts requested in the anterior to posterior direction in the patients who were immobilized, 5.1% (9 out of 175) vs. 12.6% (13 out of 103) (p < 0.05, two tailed chi-square test). There was no significant improvement in the reproducibility of isocenter placement in the cephalad to caudal or right to left directions. CONCLUSIONS: This custom-made hemibody foam cradle appears to improve the reproducibility of patient setup during the 7-week course of fractionated external beam irradiation for patients with adenocarcinoma of the prostate. This type of immobilization device is now routinely used in our clinic and is recommended for all patients receiving pelvic radiotherapy. These devices are likely to be particularly useful when contemplating dose escalation to minimize the volume of bladder and rectum included in the treatment fields.

Adenocarcinoma↗
PubMed1995

Hematologic toxicity during craniospinal irradiation: the impact of prior chemotherapy.

The purpose of this work was to determine the frequency of hematologic toxicity during craniospinal radiation (CSI) and the impact of preirradiation chemotherapy on this frequency. The charts of 37 patients who received CSI were reviewed. Twenty did not have prior chemotherapy (CT-), while 17 did receive 1 to 18 (mean 5) cycles of multi-agent systemic chemotherapy (CT+). Leukopenia/thrombocytopenia necessitating treatment interruptions occurred in 1/20 (5%) in the CT- group, compared to 8/17 (47%) among the CT+ group. This difference was statistically significant, P < 0.0001 (Fisher's exact two-tailed test). The duration of treatment interruption in the CT+ patients was 4-24 days (mean 14). Compared to the CT- group, the CT+ group had a statistically significant greater decline in their white blood cell count (WBC), platelet count, and hematocrit (HCT) during CSI (percent reduction per Gy; (P = 0.018, 0.006, and 0.047, respectively). Although not statistically significant, the CT+ group also experienced lower nadir ratios (nadir count/baseline count) in terms of WBC and platelets (P = 0.07 and 0.22, respectively). While the mean pretreatment baseline blood counts were lower in the CT+ group compared to the CT- group, these differences reached statistical significance for the HCT (P = 0.02), but not the WBC (P = 0.59) or platelets (P = 0.43). Leukopenia and thrombocytopenia are very common in patients who receive craniospinal irradiation following multi-agent systemic chemotherapy. This appears to be due to more rapid and marked reductions in counts during CSI. Since this toxicity may cause treatment interruptions that are potentially therapeutically disadvantageous, aggressive hematologic support with transfusions and growth factors may be necessary. This problem may become more common as combined modality therapy is used more frequently.

Adolescent↗
PubMed1994

The impact of conventional plus high dose chemotherapy with autologous bone marrow transplantation on hematologic toxicity during subsequent local-regional radiotherapy for breast cancer.

BACKGROUND: Forty patients with Stage II-III breast cancer with 10 or more positive axillary nodes were treated with mastectomy followed by four cycles of standard dose CAF (cytoxan, Adriamycin, 5-FU), followed by high dose cytoxan, cisplatin, carmustine (HDCT) with autologous bone marrow transplant support (ABMT), and local-regional radiotherapy (LR XRT). During LR XRT, the hematologic toxicity experienced by these patients appeared more severe than that usually seen in patients not heavily pretreated with chemotherapy. Radiation therapy was interrupted in four patients (10%) because of thrombocytopenia and leukopenia. This observation prompted a comparison of the hematologic changes seen in this group with those seen in patients not treated previously with chemotherapy. METHODS: A detailed analysis of changes in hematologic parameters during LR XRT was performed in 33 evaluable patients who received CAF-HDCT/ABMT and compared with a "control" group of 17 women who did not receive prior chemotherapy. RESULTS: The mean pretreatment leukocyte, platelet, and hematocrit counts were lower in the CAF-HDCT/ABMT group than in the control group, with the differences indicating statistical significance for the latter two (P = 0.17, P < 0.001, and P = 0.001, respectively). None of the control patients required a treatment interruption because of hematologic toxicity, whereas four of the CAF-HDCT/ABMT patients did. Among the CAF-HDCT/ABMT patients, a leukocyte count nadir of less than 2.0, a platelet nadir of less than 50,000, and a hematocrit nadir of less than 25 occurred in 12%, 19%, and 9%, respectively. The corresponding rates of control patients were 6%, 0%, and 0%, respectively. Relative to their pretreatment levels, however, both groups experienced similar declines in platelet and leukocyte counts. CONCLUSION: The higher rate of hematologic toxicity observed in the patients who previously received conventional chemotherapy plus HDCT/ABMT appears to have been due primarily to lower preradiotherapy blood counts.

Adenocarcinoma↗
PubMed1994

Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis.

PURPOSE: To determine whether plasma transforming growth factor-beta (TGF-beta) levels measured before and during radical radiotherapy for lung cancer could be used to predict patients at risk for the development of radiation pneumonitis. METHODS AND MATERIALS: The first eight patients with lung cancer (nonsmall cell: seven, small cell: one) enrolled in a prospective study designed to evaluate physiological and molecular biologic correlates of radiation induced normal tissue injury are described. The study began in June 1991. All patients were treated with radiotherapy with curative intent. Plasma transforming growth factor-beta levels were obtained before, weekly during, and at each follow-up after treatment. Pretreatment pulmonary function tests and single photon emission computed tomography scans were obtained to assess baseline lung function and were repeated at follow-up visits. Dose-volume histogram analyses were performed to determine the volume of lung which received > or = 30 Gy. Patients were assessed at each follow-up visit for signs and symptoms of pneumonitis. RESULTS: Five patients developed signs and/or symptoms of pulmonary injury consistent with pneumonitis and three patients did not. In all three patients not developing pneumonitis, plasma TGF-beta levels normalized by the end of radiotherapy. In contrast, four out of five patients who suffered pneumonitis had persistently elevated plasma TGF-beta levels by the end of therapy. This finding appeared to be independent of the volume of irradiated lung. CONCLUSIONS: These results suggest that plasma TGF-beta levels during treatment may be useful to determine which patients are at high risk of developing symptomatic pneumonitis following thoracic radiotherapy. This finding may have implications when planning additional therapy (either chemotherapy or radiotherapy) which may have potentially adverse consequences on the lung.

Adult↗