The accuracy of dynamic wedge dose computation in the ADAC Pinnacle RTP system.

The nonphysical wedge is a modality that uses computer-controlled jaw motion to generate wedge-shaped dose distributions. There are Varian enhanced dynamic wedges (EDWs) and Siemens virtual wedges (VWs). We recently commissioned dynamic wedges on both Varian and Siemens LINACs. The beam data, acquired with a Wellhofer chamber array and a Sun Nuclear profiler, are used for modeling in the ADAC Pinnacle system. As recommended by ADAC, only a limited number of beam data is measured and used for beam modeling. Therefore, the dose distributions of dynamic wedges generated by Pinnacle must be examined. Following the commissioning of the dynamic wedges, we used Pinnacle to generate a number of dose distributions with different energies, wedge angles, field sizes, and depths. The computed data from Pinnacle are then compared with the measured data. The deviations of the output factor in all square and rectangular fields are mostly within 2.0% for both EDW and VW. For asymmetric fields, the deviations are within 3%. However, exceptions of differences more than 3% have been found in a larger field and large wedge combinations. The precision of the beam profiles generated by Pinnacle is also evaluated. As a result of this investigation, we present a scope of quality assurance tests that are necessary to ensure acceptable consistency between the delivered dose and the associated treatment plan when dynamic wedges are applied.

Androgen receptor antigen density and S-phase fraction in prostate cancer: a pilot study.

PURPOSE: To determine whether quantitative flow cytometric androgen receptor density expression (MFC ratio) in prostate cancer was associated with S-phase fraction. METHODS: Flow cytometry was performed to determine DNA aneuploidy, S-phase fraction, percentage of androgen receptor (AR)-positive cells, and MFC ratio in prostate cancer patients. RESULTS: MFC ratio showed distinct clustering. Eight patients had a low MFC ratio of 1.78-2.74, while 10 patients had high MFC ratios between 4.99 and 6.48. The S-phase fraction had average values of 11.05 vs 4.92 in tumors with high vs low MFC ratio (P<0.01). CONCLUSION: S-phase fraction was significantly higher in tumors with high AR density.

A novel applicator for low-dose-rate brachytherapy of gynecological cancers.

The standard low-dose-rate (LDR) delivery system utilized in the definitive management of patients with cervical carcinoma involves an intrauterine tandem and a pair of vaginal colpostats (ovoids). This well-known application system may deliver inadequate dosage if the tumor extends to the lower vaginal mucosa. During the gauze packing of the ovoids, either operator error or narrowing of the vaginal apex can result in mal-alignment of the colpostats and subsequent inadequate dosing to the ecto-cervix. A novel vaginal cylinder has been designed to address these concerns. Beginning January 1, 2001, patients with cancer of the cervix, endometrium, or vagina requiring LDR brachytherapy have been enrolled into an institutionally sanctioned clinical trial. As of May 31, 2001, a total of 11 patients have been entered but only 10 were successfully implanted with the test device. Patient follow-up has ranged from 0.81 years to 1.2 years (median: 0.96 years). Using our study applicator, all patients received within 10% of the preimplant prescribed dose to tumor. Also, no one had cumulative dosage that exceeded 10% of the maximum allowed dose to the critical normal tissues. Thus far, all study patients have had no clinical evidence of persistence/recurrence of disease or complications from treatment. The preliminary results presented herein clearly demonstrate the feasibility of this novel LDR vaginal cylinder in the treatment of a variety of clinical situations involving gynecological cancers. Our institutional trial is continuing.

Twice-daily prophylactic cranial irradiation for patients with limited disease small-cell lung cancer with complete response to chemotherapy and consolidative radiotherapy: report of a single institutional phase II trial.

Prophylactic cranial irradiation (PCI) has been demonstrated to significantly reduce the incidence of brain relapse from limited disease small-cell lung cancer (LD SCLC), but concerns about neurologic toxicity remain. The purpose of this report was to update a phase II institutional trial that explored the impact of twice-daily PCI on neurologic toxicity as well as outcome for this group of patients. All eligible subjects had documented complete response to induction chemotherapy and consolidative chest irradiation. The whole brain was treated with twice-daily fractions of 1.5 Gy with megavoltage irradiation to an approximate total dose of 30.0-36.0 Gy. Although not devised as a randomized study, approximately half of the eligible patients declined the protocol enrollment of their own volition and were retrospectively evaluated as a "historical" control group regarding the incidence of brain metastases. Fifteen patients accepted twice-daily PCI, with 12 deferring treatment. Median follow-up was 20 months. Disease-free survival at 2 years was 54% with twice-daily PCI versus 0% without any PCI (p = 0.013). Overall survival at 2 years was 62% with twice-daily PCI versus 23% without PCI (p = 0.032). No statistically significant neurologic deterioration was detected in the PCI group posttreatment. Thus, twice-daily PCI should be considered for patients with LD SCLC who achieve a complete response to chemoirradiation. A multi-institutional randomized trial would be necessary before making definitive recommendations.

The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy.

PURPOSE/OBJECTIVES: To determine whether the use of mild soap and aloe vera gel versus mild soap alone would decrease the incidence of skin reactions in patients undergoing radiation therapy. DATA SOURCES: Prospective, randomized, blinded clinical trial. SETTING: Radiation therapy outpatient clinic in a cancer center affiliated with a major teaching medical facility. SAMPLE: The mean age of the participants was 56 years. The group consisted of Caucasians (74%) and African Americans (26%). The ethnic mix was non-Hispanic (65%) and Hispanic (35%). METHODS: Prophylactic skin care began on the first day of radiation therapy. Patients cleansed the area with mild, unscented soap. Patients randomized into the experimental arm of the trial were instructed to liberally apply aloe vera gel to the area at various intervals throughout the day. FINDINGS: At low cumulative dose levels < or = 2,700 cGy, no difference existed in the effect of adding aloe. When the cumulative dose was high (> 2,700 cGy), the median time was five weeks prior to any skin changes in the aloe/soap arm versus three weeks in the soap only arm. When the cumulative dose increases over time, there seems to be a protective effect of adding aloe to the soap regimen. IMPLICATIONS FOR NURSING PRACTICE: Skin products used to treat radiation dermatitis vary among institutions. Nurses should be aware that some patients may be predisposed to skin problems. Nurses must be aware of newly developed products and research regarding these products so that effective treatment can be instituted.

Radiation recall dermatitis induced by methotrexate in a patient with Hodgkin's disease.

Radiation recall dermatitis refers to an inflammatory skin reaction at a previously irradiated field subsequent to chemotherapy administration. A number of antineoplastic agents have been reported to cause this phenomenon. We observed radiation recall dermatitis in a patient with stage IV nodular sclerosing Hodgkin's disease after methotrexate therapy for acute graft-versus-host disease (GVHD) prophylaxis. The patient had previously undergone matched related bone marrow transplantation with busulfan and cyclophosphamide as a preparative regimen. Subsequently, she received cyclosporine and methotrexate for acute GVHD prophylaxis. Two areas of skin previously irradiated to 3,000 cGy developed radiation recall dermatitis after two doses of methotrexate given 2 days apart and exacerbated by the third and fourth doses. This reaction occurred 34 days after the last dose of radiation therapy (RT). We believe this is the first case of radiation recall dermatitis after methotrexate therapy. Given the increased use of methotrexate in several neoadjuvant and adjuvant protocols in association with RT, its potential to produce radiation recall reactions should be considered.

Early MRI findings in high grade glioma.

Magnetic resonance imaging (MRI) is more sensitive than computerized tomography in the detection of many intracerebral lesions; however, the significance of some MRI findings may be unclear. Over four years, nine patients, aged 40-79 years, have been encountered whose initial MRI scans were negative or had minimal abnormalities and soon thereafter had high grade glioma. Initial MRI was performed in eight patients for new-onset seizures and one patient for a focal deficit. MRI was negative in four of the patients and mildly abnormal in five of the patients (small areas of increased T2 and/or minimal enhancement). The initial diagnoses usually included inconclusive differentials of stroke and infection with neoplasm less frequently considered. Radiographic progression leading to the diagnosis of high grade glioma became evident on repeat MRI in 1-8 months with six patients showing progression within three months. All patients underwent surgery and had histologic diagnosis of glioma. Although MRI is quite sensitive, four of the initial scans were negative with reasonable quality studies. Conversely, in five of the initial scans, the tumors were detected when so small that the radiographic findings were not typically diagnostic. Glioma must be considered as a possible cause of initial seizures or new neurologic deficits in adults with normal or minimally abnormal MRI. In this group, seizures were the overwhelming hallmark of presentation. In such a clinical situation, close follow-up with short interval repeat MRI should be performed.

Intraoperative echographic localization of iodine-125 episcleral plaque for brachytherapy of choroidal melanoma.

PURPOSE: To report intraoperative echographic localization of iodine-125 episcleral plaque for brachytherapy of choroidal melanoma. METHODS: In a retrospective study, 117 eyes with medium-sized choroidal melanoma in 117 patients not participating in the Collaborative Ocular Melanoma Study underwent iodine-125 episcleral plaque radiotherapy with intraoperative echographic verification of plaque placement between January 1992 and December 1998 at the Bascom Palmer Eye Institute. RESULTS: After initial plaque placement using standard localization techniques, intraoperative echography demonstrated satisfactory tumor-plaque apposition in 76% of eyes (89 of 117). In the 28 eyes (28 of 117, 24%) that required repositioning of the plaque, the extent of misplacement was less than 1 mm in 10 eyes, 1.1 to 3.0 mm in six eyes, and greater than 3 mm in eight eyes. Two eyes had tilting of the plaque, and in two additional eyes, although the plaque covered all tumor margins, the centration was considered suboptimal. Repositioning was necessary in 1 eye with an anteriorly located tumor (1 of 13, 7.7%) and in 20 eyes with peripapillary or posterior pole tumors (20 of 67, 26.3%). Anteriorly located tumors required plaque repositioning significantly less frequently than did posteriorly located tumors (P = .041). Misalignment involved one tumor margin in 23 eyes and two margins in five eyes. The most commonly misaligned margins were the lateral (35%) and posterior margins (26%). In no case was an anterior marginal misalignment documented. At a mean follow-up of 37 months, no tumor-related death or metastatic disease was noted. Two of the 117 patients (1.7%) had local tumor recurrence and underwent enucleation. CONCLUSIONS: Intraoperative echography is an effective adjunct for localization and confirmation of tumor-plaque relationship. This technique facilitates the identification and correction of suboptimal plaque placement at the time of surgery, potentially minimizing treatment failures.

Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406.

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study. METHODS AND MATERIALS: Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion > or = 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5-10 mm around the prostate for patients in Group 1 and 5-10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5-10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a > or = grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used. RESULTS: Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53-54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0-3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81-85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected (p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected (p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving > or = 65 Gy was more than 30% (p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy (p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving > or = 65 Gy increased (p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc (p = 0.019). CONCLUSION: Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a co

Prognostic factors and survival in patients with spinal cord gliomas after radiation therapy.

The purpose of this study was to determine the impact of various prognostic factors on survival in spinal cord gliomas treated with radiation. Fifty-three patients with spinal cord gliomas irradiated at three major institutions were studied. Fifty-one patients were classified as having ependymoma, astrocytoma, or both. Two patients were classified as having gliomas (otherwise unspecified). Eleven patients had complete resection of their tumor. Biopsy or partial resection was done in the remaining patients. All patients received external beam radiation. Information on these patients was placed in a central database file and analyzed for the effect of several prognostic factors on survival. Overall survival of the entire group was 76.9% and 61.5% at 5 and 10 years, respectively. Pathologic status significantly affected survival (p = 0.03). Patients with ependymomas had a 5-year survival of 93.8% and a 10-year survival of 67.5%. Patients with astrocytoma had a 5-year survival of 64.2% and a 10-year survival of 54%. Univariate analysis showed pathology and the presence of cysts (p = 0.038) to significantly affect survival. Age, sex, location of the primary, extent of surgery radiation dose, and number of involved segments did not affect survival. On multivariate analysis, astrocytic pathology, involvement of more than five segments, male sex, and the absence of cysts (in or adjacent to the tumor) were associated with a significantly inferior survival. This study confirms the importance of pathology and number of segments involved in determining outcome or survival. The presence of cysts adjacent to or within the tumor was found to be associated with an improvement in survival.

External beam radiotherapy in retinoblastoma: tumor control and comparison of 2 techniques.

OBJECTIVE: To investigate eye conservation, local control, and complication rates among children with retinoblastoma treated with 2 different external beam radiotherapy (EBR) techniques. METHODS: Fifty-eight eyes in 42 patients received EBR as the primary treatment modality for retinoblastoma (median follow-up, 37 months). The EBR technique was relative lens-sparing (RLS) in 26 eyes and modified lateral beam (MLB) in 32 eyes. Both groups were comparable in Reese-Ellsworth retinoblastoma classification. If necessary, patients received focal salvage therapy. RESULTS: At 24 months, eye conservation rates were 88.5% and 89.1% among eyes treated with RLS and MLB, respectively (P = .40); tumor control rates without salvage therapy were 84.6% and 53.3% (P = .02), respectively. Among eyes with Reese-Ellsworth stage IV and V disease, eye conservation rates were 88%+/-8% and 83%+/-9% at 36 months in the RLS and MLB groups, respectively, and local tumor control rates were 81%+/-10% and 51%+/-12%. Percentages of eyes without cataract at 36 months were 83.1% and 63.0%, respectively (P = .40). Among patients observed for at least 18 months, midfacial hypoplasia developed in 38.5% and 29.4%, respectively (P = .70). CONCLUSIONS: The EBR technique was associated with high eye conservation and local control rates. Salvage therapy was performed significantly less frequently in the RLS group compared with the MLB group, and complication rates in both groups were similar.

A comparison of 3-D data correlation methods for fractionated stereotactic radiotherapy.

PURPOSE: Stereotactic radiosurgery is currently used to treat patients who are not good candidates for conventional neurosurgical procedures. For treatments of nonvascular tumor cells, it appears that fractionation offers a radiobiological advantage between tumor and normal tissues. Therefore, fractionated stereotactic radiotherapy (FSR) is preferred because it minimizes normal tissue complications and maximizes local tumor control probability. We have implemented a methodology clinically to perform the noninvasive patient repositioning technique. The 3-D data correlation method for high-precision and multiple fraction stereotactic treatments has been presented. METHODS AND MATERIALS: Three different optimization algorithms (Hooke and Jeeves optimization, simplex optimization, and simulated annealing optimization) are evaluated to calculate the transformation parameters necessary for FSR. A least-square object function is created to perform the 3-D data matching process. By minimizing the unconstrained object function value the best fit can be approached for the reference 3-D data sets. Simulation shows that these algorithms deliver results that are comparable to the previously published correlation algorithm (1,2) (singular value decomposition [SVD] method). The advantage for optimization algorithms is easily understood and can be readily implemented by using a personal computer (PC). The mathematical framework provides a tool to calculate the transformation matrix which can be used to adjust patient position for fractionated treatments. Therefore, using these algorithms for a high-precision fractionated treatment is possible without an invasive repeat fixation device and has been implemented clinically. A bite plate system was incorporated to acquire 3-D patient data. With a 3-D digital camera localization device, the patient motion can be followed in real time with the system calibrated to the isocenter. RESULTS: Two types of data sets are utilized to study the correlation results. One is using the digitized patient data which were retrieved clinically. The other is using the randomly generated data sets. Simulation errors for the optimization algorithms are all less than 1 mm in translation and less than 1 degree in rotation. Currently, FSR is performed using special designed repeat fixation devices which assure reproducible patient position for multiple fractions of radiation treatment. Clinical results indicated that this technique provided excellent treatment results. CONCLUSION: Three optimization algorithms have been applied and evaluated in calculating the transformation parameters between two 3-D contours or digitized data points. The mathematical functions behind these optimization algorithms are straightforward and can be easily implemented. When incorporated with the proper CT/MR image data with an electronic portal imaging (EPI) system, this process can possibly verify the patient's treatment position whenever there is doubt about the movement during the treatment procedure.

Bladder and rectal doses from external-beam boosts after gynecologic brachytherapy.

PURPOSE: To establish a typical value for radiation doses under pelvic midline shields. MATERIALS AND METHODS: Three methods were used to determine bladder and rectal doses under 5- or 6-half-value layer (HVL) shields for 10- and 24-MV external beams. First, dose was computed with a standard irregular field routine in 25 consecutive patients (aged 35-70 years) with stage IIB or IIIB disease treated with cesium-137 brachytherapy followed by a parametrial external-beam boost. Second, in vivo measurements with a solid-state probe were recorded during the first boost after completion of brachytherapy in each patient. Third, measurements obtained with an ionization chamber in a solid phantom (water-equivalent material) were compared with computed and in vivo results. RESULTS: All three dosimetric methods yielded bladder and rectal doses higher than the commonly assumed 5% of the unshielded primary beam dose. Doses within the shielded volume may be as high as 15% of the unshielded dose. Doses are similar under 5- and 6-HVL midline shields. Often, the actual bladder and rectal doses exceeded the planned dose limits and their corresponding maximum radiation dose tolerance levels. CONCLUSION: Bladder and rectal doses are higher than previously understood. Parametrial boosts may contribute as much as 3.0 Gy to the bladder and rectal doses.

Gamma knife radiosurgery for large volume brain tumors: an analysis of acute and chronic toxicity.

Gamma Knife radiosurgery is often used to treat intracranial tumors <4 cm (approximately 13.5 cm3) in mean diameter. Larger lesions are rarely treated because of the expectation that increasing target volume will increase toxicity. We retrospectively analyzed 35 patients with primary or metastatic brain tumors of more than 13.5 cm3 treated with the Gamma Knife. Only 3 (8.5%) patients developed acute clinical toxicity. Nine (25%) patients developed post-Gamma Knife radionecrosis based on imaging studies, with only 3 of these patients (9% of the study population) having clinical progression of symptoms. Necrosis was not found to be related to prescribed dose, treatment volume or number of treated isocenters. We found no undue toxicity from the treatment of large brain tumors with the Gamma Knife.

Dose volume histogram analysis of the gamma knife radiosurgery treating twenty-five metastatic intracranial tumors.

Treating multiple brain metastatic sites in Gamma Knife radiosurgery is not uncommon. Most metastases can be treated with few or even one single shot. Occasionally we have patients returning for retreatment for different intracranial metastatic sites at different times. Dose distribution for these metastases are prescribed locally without considering the previous dose contribution. We present a study which simultaneously calculates the dose distribution of 25 randomly placed shots distributed inside the intracranial region. The Dose Volume Histogram (DVH) is plotted to study the coverage of the tumor sites and normal tissues. We have calculated ten DVH studies and show that 50% of the brain volume receives less than 500 cGy for the maximum tumor dose of 40 Gy, and the dose gradient is extremely steep. This DVH analysis shows that the Gamma Knife radiosurgery is a good treatment modality to control the local tumors while maintaining normal brain function, even for the large number of brain metastasis treated at different times.

Does a radiation dose-response relation exist concerning survival of patients who have soft-tissue sarcomas of the extremities? Radiation dose-response relation for soft-tissue sarcomas.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

The importance of postoperative radiation therapy in multimodality management of locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery, and radiation.

PURPOSE: To determine the impact of postoperative radiation on locoregional relapse and overall survival rate in a multimodality protocol for locally advanced breast cancer (LABC). MATERIAL AND METHODS: Of the patients entered in the protocol, 55 were evaluable. Treatment consisted of: neoadjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) until a maximum response had been achieved; modified radical mastectomy; 6 courses of postoperative adjuvant MVAC chemotherapy, and chest wall irradiation (CWXRT). Multivariate analysis of locoregional response and overall survival was done. RESULTS: Of the total, 42 patients received chest wall radiation; 28 of these also received radiation to regional lymph nodes. Chest wall doses ranged from 45 Gy to 50.4 Gy to the whole chest wall, with 31 patients receiving an additional chest-wall boost. The incidence of locoregional relapse with and without radiation was 7% vs. 31%, respectively (p = 0.026). An overall survival benefit was seen in those receiving radiation, with a mean overall survival of 50 months vs. 20 months, and a 3-year overall survival of 88% vs. 46% with and without radiation, respectively (p = 0.003). Multivariate analysis showed that overall survival was affected by the presence of pathological CR (p = .047), the number of pre-operative chemotherapy cycles (p = .036) and whether or not they received radiation (p = 0.003). Neither the interval between surgery and radiation, technique of radiation, nor radiation modality significantly affected local control. CONCLUSION: The significant improvement in local regional control and overall survival with the addition of radiation suggests that radiation should be an integral part of multimodality management of locally advanced breast cancer.

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.

Dose-volume histograms for bladder and rectum.

PURPOSE: A careful examination of the foundation upon which the concept of the Dose-Volume Histogram (DVH) is built, and the implications of this set of parameters on the clinical application and interpretation of the DVH concept has not been conducted since the introduction of DVHs as a tool for the quantitative evaluation of treatment plans. The purpose of the work presented herein is to illustrate problems with current methods of implementing and interpreting DVHs when applied to hollow anatomic structures such as the bladder and rectum. METHODS AND MATERIALS: A typical treatment plan for external beam irradiation of a patient with prostate cancer was chosen to provide a data set from which DVH curves for both the bladder and rectum were calculated. The two organs share the property of being shells with contents that are of no clinical importance. DVHs for both organs were computed using a solid model and using a shell model. Typical treatment plans for prostate cancer were used to generate DVH curves for both models. The Normal Tissue Complication Probability (NTCP) for these organs is discussed in this context. RESULTS: For an eight-field conformal treatment plan of the prostate, a bladder DVH curve generated using the shell model is higher than the corresponding curve generated using the solid model. The shell model also has a higher NTCP. A six-field conformal treatment plan also results in a higher DVH curve for the shell model. A treatment plan consisting of bilateral 120-degree arcs, results in a higher DVH curve for the shell model, as well as a higher NTCP. CONCLUSION: The DVH concept currently used in evaluation of treatment plans is problematic because current practices of defining exactly what constitutes "bladder" and "rectum." Commonly used methods of tracing the bladder and rectum imply use of a solid structure model for DVHs. In reality, these organs are shells and the critical structure associated with NTCP is obviously and indisputably the shell, as opposed to its contents. Treatment planning algorithms for DVH computation should thus be modified to utilize the shell model for these organs.

Hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and mitomycin-C (+/- granulocyte-colony stimulating factor) in the treatment of patients with locally advanced head and neck carcinoma.

BACKGROUND: The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control. In an attempt to reduce acute mucosal and hematologic toxicity, granulocyte-colony stimulating factor (G-CSF) was added during the second phase of this study. METHODS: Seventy patients (53 with Stage IV and 17 with Stage III disease) were entered between May 1988 and June 1995 into a Phase I/II trial of concurrent radiation therapy (74.4 gray (Gy) total dose; 1.20 Gy twice daily), 5-fluorouracil (1000 mg/m2/24 hours for 72 hours), and cisplatin (50 mg/m2) for 3 cycles with the addition of mitomycin C (8 mg/m2) in Cycle 2. G-CSF was added after the initial entry of 34 patients. RESULTS: At a median follow-up of 41 months (range, 12-80 months), 44 patients were alive with a projected median overall survival of 54 months. Grade 3/4 mucositis, observed in 65% of patients, was equally prevalent and prolonged in both G-CSF-treated (+) and G-CSF-naive (-) patients. Grade 3/4 leukopenia was present in 45% and 36% of G-CSF- and G-CSF+ patients, respectively. The 3-year locoregional control and cause specific survival rates were 68% and 75%, respectively. CONCLUSIONS: This regimen was feasible and effective but caused severe mucositis. No benefit was derived from the addition of G-CSF. This regimen deserves further modification to reduce acute mucositis toxicity yet maintain the high locoregional control rate.