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L R Coia

Publications and source records attributed to L R Coia.

At least 37 records · Page 2Linked to original sources
PubMed1997

Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study.

PURPOSE: The development of conformal radiation technique including improved patient immobilization has allowed us to test the value of dose escalation in optimizing the radiation treatment of prostate cancer. METHODS AND MATERIALS: Outcome is reported for 233 consecutive patients treated with conformal technique between March 1989 and October 1992. Dose was escalated from 68 Gy to 79 Gy. Patient status is reported at 3 years follow-up, which is available in all alive patients. Pretreatment and serial posttreatment prostate specific antigen (PSA) values are available for all patients. Biochemical freedom of disease (bNED) defines failure as PSA > 1.5 ngm/ml and rising on two consecutive measures. Dose response for bNED control of cancer and late morbidity are represented by logit response models fitted to the data. Kaplan-Meier methods, the log rank test, and Cox Regression models are also used. RESULTS: No dose response is observed for bNED survival for patients with pretreatment PSA <10 ngm/ml comparing patients treated above or below 71.5 Gy or on multivariate analysis. Dose response is observed for bNED survival for pretreatment PSA groups of 10-19.9 ngm/ml and 20+ ngm/ml. The dose associated with 50% bNED survival at 3 years is 64 Gy and 76 Gy, respectively. The slope of the dose responses are 13 and 9%, respectively. Dose response is demonstrated for Grade 2 gastrointestinal (GI), Grade 2 genitourinary (GU), and Grade 3,4 combined GI and GU late morbidity. The slopes of the morbidity responses are steeper than for cancer control (19 to 21%). CONCLUSIONS: Patients with pretreatment PSA < 10 ngm/ml do not benefit from dose escalation, and the serious late morbidity of conformal radiation at 70 Gy is < 3%. Patients with PSA values 10-19.9 ngm/ml and 20+ ngm/ml benefit from dose escalation beyond 70 Gy. Treatment beyond 75 Gy results in > 10% serious morbidity unless special precautions are taken to protect the rectal mucosa. All levels of severity of radiation morbidity show a dose response and combined with the dose response for bNED survival these data allow the optimization of treatment.

Disease-Free Survival↗
PubMed1997

Effect of low-density lateral interfaces on soft-tissue doses.

PURPOSE: Doses at the interface between tissue and low-density inhomogeneities with the interface positioned perpendicular to the beam direction have been well studied. When the inhomogeneity lies parallel to the beam direction (i.e., a lateral interface), the resulting dose distribution is not as well known. Lateral lung-soft-tissue interfaces are common in many fields used to treat malignancies in the thorax region including tangential breast fields and anteroposterior fields for lung and esophageal cancer. The purpose of this study was to evaluate the dose distribution along lateral interfaces and to determine the implications for treatment. METHODS AND MATERIALS: A polystyrene and cork slab phantom was irradiated from the side to simulate treatment fields with lateral lung-soft-tissue interfaces. The beam was positioned with the isocenter in polystyrene and the field edge in cork. Cork slabs (0.6-2.5 cm) were used to simulate different thicknesses of lung between the field edge and the target volume. Measurements were made using a parallel plate ionization chamber. With the chamber position held constant, polystyrene slabs were added between the cork and the chamber to study the dose distribution in the interface region. Interface doses were studied as a function of the amount of cork in the field, field size, beam energy (6-18 MV), and depth. RESULTS: Doses in the interface region were lower by as much as 10% compared to doses in a homogeneous phantom. For a given cork width and field size, the magnitude of the underdose increased by several percent as the x-ray energy increased from 6 to 18 MV. The underdose at the interface was 5% for 6 MV and 8% for 18 MV X-rays with a 1-cm cork width. For a 2.5-cm cork width, underdoses of 2.5% and 3% at distances up to 2.5 and 4 mm lateral to the interface were observed for 6- and 18-MV X-rays, respectively. However, doses right at the interface were 1% greater for 6 MV and 3% less for 18 MV than doses in a homogeneous phantom. For a given cork width, the interface doses were not significantly dependent on field width but decreased by an additional 2-3% as the length decreased to 4 cm. Additional decreases were also observed when the measurement depth decreased to 3 cm. With a 1-cm width of cork in the field, a lateral distance of 3-4 mm from the interface was necessary to ensure doses of at least 98% of the homogenous dose with 6-MV X-rays. A lateral distance of 6-7 mm was necessary for 10- and 18-MV X-rays. CONCLUSION: Underdosing will occur in the soft tissues adjacent to low-density inhomogeneities. The magnitude depends primarily on the width of the inhomogeneity seen in the treatment field, but also on field size, depth, and beam energy. For treatment fields with a lateral lung interface, a segment of tissue approximately 3-4 mm thick for 6 MV and 6-7 mm thick for higher-energy beams may be underdosed. Lung widths of > or = 1.75 cm as observed on film will generally guarantee doses of at least 96% of those calculated with no inhomogeneity corrections. High-energy beams are often used to treat sites in the thorax or breast to improve dose homogeneity throughout the treatment volume. Potential underdosing due to the presence of lung should be considered and may require a decrease in beam energy or an increase in the margin between the target volume and the field edge to ensure adequate treatment.

Connective Tissue↗
PubMed1997

Treatment planning for adenocarcinoma of the rectum and sigmoid: a patterns of care study. PCS Committee.

PURPOSE: To conduct a study of the process of treatment planning and treatment of adenocarcinoma of the rectum and sigmoid in the United States, and to compare survey results to consensus guidelines. METHODS AND MATERIALS: A consensus committee developed guidelines for the radiotherapeutic management of adenocarcinoma of the rectum and sigmoid, and also developed a survey form that was used to gather data to evaluate the practice patterns for patients treated in 1989 and 1990 against the consensus guidelines. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the US: 21 academic, 26 hospital based, and 26 free standing. During the site visits, the radiotherapy records were examined by the surveyor physicist and radiation oncologist to extract and record the required data. Data collected included items related to treatment specific parameters, including treatment planning considerations. Analyses included stratification as to the types of institutions, academic, hospital based, or free standing. RESULTS: For many treatment parameters there are discrepancies between the patterns of practice determined by the surveys and the consensus guidelines for radiotherapy treatment of adenocarcinoma of the rectum and sigmoid. Significant differences in practice among the stratified institution types were found in only a few parameters.

Adenocarcinoma↗
PubMed1997

Neck failure in T2N0 squamous cell carcinoma of the true vocal cords: the Fox Chase experience and review of the literature.

There is a need for additional data in the literature regarding elective nodal irradiation in the treatment of T2N0 squamous cell carcinoma of the glottic larynx. We examined the experience at the Fox Chase Cancer Center and performed a literature review in order to define a treatment policy. Sixteen patients with T2 squamous cell carcinoma of the glottic larynx were treated with radiation therapy. Ten patients were irradiated to the larynx alone and six to the larynx and regional nodes. None of the patients in our series experienced a nodal recurrence regardless of whether the neck was electively irradiated. A literature review of 413 patients revealed that 2.6% of patients who did not have their nodes electively irradiated and had their primary tumor controlled experienced a nodal failure compared to 3.7% if the primary and regional nodes were irradiated (P = 0.88). Similarly, there was no significant difference in the rate of nodal failure for patients who experienced a recurrence at the primary site regardless of whether they received elective nodal irradiation (P = 0.36). We recommend treatment to the larynx alone since our policy is to treat the regional nodes only when the incidence of occult lymphadenopathy in the neck exceeds 15%.

Carcinoma, Squamous Cell↗
PubMed1997

Combined-modality therapy for esophageal cancer: phase I trial of escalating doses of paclitaxel in combination with cisplatin, 5-fluorouracil, and high-dose radiation before esophagectomy.

Several recent reports support administering preoperative chemotherapy and radiotherapy to improve the outcome of patients with resectable esophageal malignancies. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), 5-fluorouracil (5-FU), and cisplatin are known radiosensitizers, and paclitaxel has demonstrated single-agent activity in patients with metastatic esophageal cancer. This study sought to define the maximum tolerated dose of paclitaxel given with 5-FU, cisplatin, and 60 Gy radiotherapy before esophagectomy to patients with potentially resectable lesions. Seventeen patients so treated underwent esophagectomy. Three patients with metastatic disease, treated to obtain more information about the toxicity of the combined-modality regimen, did not undergo surgery. Over 6 weeks, 60 Gy radiation was administered in 2-Gy fractions. During radiation treatment, continuous intravenous infusions of 5-FU 225 mg/m2/d were administered, with paclitaxel given weekly as a 1-hour intravenous infusion immediately preceding a 1-hour cisplatin infusion. Surgery was performed 4 to 6 weeks after the completion of radiotherapy. The 27 patients, one of whom was a woman, had a median age of 58 years and an Eastern Cooperative Oncology Group performance status of 0 (10 patients) or 1. Three patients had a squamous cell histology, while 22 had adenocarcinoma; two had other histologies. The paclitaxel dose levels were 25 mg/m2 in four patients, 40 mg/m2 in five patients, 60 mg/m2 in nine patients, and paclitaxel 50 mg/m2 with 5-FU reduced to 200 mg/m2 in nine patients. The latter proved to be the maximum tolerated dose combination, with cisplatin held constant at 25 mg/m2. This level represents weekly dose intensities of 9.6 Gy radiation, 48 mg/m2 paclitaxel, 24 mg/m2 cisplatin, and 192 mg/m2 5-FU. Diarrhea in four patients, mucositis and dehydration in seven, electrolyte wasting in two, gram-positive catheter-related infection in three, and neuropathy in one proved dose limiting. Hematologic toxicity was relatively mild, with three episodes of nonneutropenic bacteremia, one of which was fatal. Postoperative chemotherapy consisting of four cycles of paclitaxel 175 mg/m2 over 3 hours and cisplatin 75 mg/m2 over 1 hour every 3 weeks was planned but rarely feasible due to postoperative morbidity and poor tolerability of postoperative chemotherapy. Therefore, the use of two induction cycles of this regimen given before the combined-modality study regimen is currently being investigated. Of 17 patients whose surgical specimens were assessed pathologically, three had complete remissions and 14 had partial remissions, five of which were characterized as very good, showing only microscopic foci and marked radiation effects. The median follow-up of the 17 patients who underwent surgery is 50 weeks (range, 5 to 111 weeks). Three relapses occurred at 26, 33, and 43 weeks. We conclude that this is an intense combined-modality preoperative regimen for patients with esophageal cancer. Determining the efficacy of this regimen will require further follow-up and the performance of phase II trials.

Adenocarcinoma↗
PubMed1996

The influence of lymphangiography on the development of hypothyroidism in patients irradiated for Hodgkin's disease.

PURPOSE: There is no consensus in the literature regarding the role of lymphangiography in promoting hypothyroidism in individuals with Hodgkin's disease irradiated with a mantle field. We sought to analyze the onset and rate of developing clinical or chemical hypothyroidism as well as possible factors related to its development in patients who received irradiation to the thyroid gland during treatment of Hodgkin's disease. METHODS AND MATERIALS: One hundred and forty-two patients with Hodgkin's disease were treated at the Fox Chase Cancer Center between June 1967 and October 1993. All patients were treated with curative intent with radiation therapy using a mantle field. After exclusion of patients without available thyroid function tests, < 200 days of follow-up, or no radiation to the thyroid, 104 patients were eligible for analysis. Follow-up ranged from 7-170 months (median: 43 months). Sixty-seven patients had a lymphangiogram. Seventy-three patients were treated with radiation alone and 31 with radiation plus chemotherapy. RESULTS: The actuarial 2-, and 5-year rates of biochemical hypothyroidism for all 104 patients were 18 and 37%, respectively. Forty patients developed hypothyroidism: 9 (23%) at < or = 1 year, 18 (45%) at < or = 2 years, and 33 (83%) at < or = 5 years. The actuarial 2-, and 5-year rates of biochemical hypothyroidism for patients who underwent a lymphangiogram were 23 and 42%, respectively, compared to 9 and 28%, respectively, for patients who received mantle irradiation without a lymphangiogram (p = 0.05). The effects of lymphangiogram, total thyroid dose, stage, chemotherapy, dose per fraction, energy, and age were evaluated for all patients by Cox proportional hazards regression analysis. The use of a lymphangiogram (p = 0.05) was the only variable that significantly influenced hypothyroidism. CONCLUSIONS: This paper demonstrates in a multivariate analysis accounting for other potentially important variables the significant effect of lymphangiography and subsequent radiation therapy on the development of hypothyroidism. This information must be balanced with the fact that lymphangiograms remain a useful aid in assessing lymph node involvement, staging patients, and planning treatment fields.

Adult↗
PubMed1996

Do overall treatment time, field size, and treatment energy influence local control of T1-T2 squamous cell carcinomas of the glottic larynx?

PURPOSE: To evaluate treatment and patient related prognostic factors that may influence local control in the treatment of T1-T2 squamous cell carcinoma of the glottic larynx. METHODS AND MATERIALS: One hundred nine patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1991. Follow-up ranged from 26-165 months (mean 83 months). RESULTS: The 2-year local control rates for patients with T1 and T2 lesions were 89% and 80%, respectively. The 2-year local control rate for patients whose overall treatment time was < 50 days was 92% vs. 82% for patients whose overall treatment time was > 50 days (p = 0.07). The 2-year local control rate for patients treated with an irradiated area < 36 cm(2) was 90% compared to 86% in patients who were treated to an area > or = 36 cm(2). The 2-year local control rate for patients treated with 60Co was 83% vs. 92% for patients treated with 6 MV x-ray. Cox proportional hazards regression analysis was performed using the following variables: treatment energy, irradiated area, gender, tobacco pack years, tumor differentiation, overall treatment time, total dose, dose per fraction, and T stage. Overall treatment time (p = 0.05) was the only variable that significantly influenced local control. CONCLUSION: Extending the overall treatment time was found to adversely influence local control. Neither the irradiated area nor treatment energy was found to influence local control in early stage vocal cord carcinoma.

Adult↗
PubMed1996

Prediction of tumour hypoxia and radioresistance with nuclear medicine markers.

Second-generation nuclear medicine markers of tumour hypoxia have been synthesised and screened for hypoxic marking activity in cell cultures and in mouse tumours (EMT-6). Markers of the iodinated azomycin nucleoside class with greater water solubility and faster plasma clearance rates relative to iodoazomycin arabinoside (IAZA) were of particular interest. The test systems used to characterise hypoxic marking activity of compounds included (1) covalent linkage of radiolabelled markers to cells in suspension culture equilibrated with specific O2 concentrations; (2) biodistribution of radiolabelled markers in EMT-6 tumour-bearing mice; and (3) biodistribution in R3327-AT tumour-bearing rats by nuclear medicine procedures. Of the iodinated azomycin nucleosides produced to date, beta-D-iodoazomycin galactoside (beta-D-IAZG) and beta-D-iodoazomycin xylopyranoside (beta-D-IAZXP) exhibited high metabolism-dependent hypoxic cell uptake, rapid clearance kinetics from the blood and excellent tumour marking activity in vivo. Tumour-blood (T/B) ratio (a measure of tumour hypoxic fraction) was dependent upon EMT-6 tumour size and implantation site. The radioresistance of individual tumours was measured by in vivo/in vitro assay and correlated well with the T/B ratio of hypoxic marker. These studies have identified beta-D-IAZG and beta-D-IAZXP as effective hypoxic markers for planar and single photon emission computerised tomography (SPECT) imaging studies of tumour oxygenation.

Animals↗
PubMed1996

Palliative radiation therapy in the United States.

In fact that radiation therapy is often the most effective means of palliating symptoms caused by cancer is well recognized in the United States. Estimates of the proportion of patients treated in the US with radiation therapy who are treated for palliative rather than curative intent range from 15% to 50% and depend on the geographic location, cancer incidence, referral patterns, etc. All radiation oncologists in the United States have had significant experience with the use of palliative radiation therapy during their residency and in their practice. Estimates from patterns of care studies indicate that over 250,000 patients were treated with palliative radiation therapy at a cost of between $1.0 and $1.8 billion in 1994. The scope of this presentation will cover four aspects of palliative radiation therapy in the United States: 1. existing practice patterns; 2. factors affecting treatment patterns; 3. the cost of palliative radiation therapy; and 4. present research and guidelines developments efforts.

Humans↗
PubMed1995

Harvesting backscatter electrons for radiation therapy.

PURPOSE: An innovative technique is used to harvest backscatter electrons for the treatment of superficial small lesions of skin, oral cavity, and rectum where a significant dose gradient and maximum surface dose is desired. METHODS AND MATERIALS: Backscatter electrons are harvested out of the primary electron beams from the linear accelerators. The design consists of a short cylindrical cone that fits snugly over a long cylindrical electron cone. The short cylindrical cone has a thick circular plate of high atomic number medium (Pb) attached to the distal end, and a lateral slit of variable length and width. The width of the slit could be closed as desired by rotating the two cones and the length can be increased by lowering the short cylindrical cone. Primary electrons strike the Pb plate perpendicularly and produce backscatter electrons that pass through the lateral slit for treatment. Using film and a parallel plate ion chamber, backscattered electron dose characteristics are studied. RESULTS: The depth dose characteristic of the backscatter electron is very similar to that of the 0.2 mm Al half-value layer x-ray beam that is commonly used for the intracavitary and superficial lesions. The backscatter electron energy is nearly constant and effectively < or = 1 MeV from the clinical megavoltage beams. The backscatter electron dose rate of 0.32-0.8 Gy/min could be achieved from modern accelerators without any modification. The beam flatness is dependent on the slit size and the depth of treatment, but is satisfactory to treat small lesions. CONCLUSIONS: The measured data for backscatter electron energy, fluence, depth dose, flatness, dose rate, and absolute dose indicates that the harvested backscattered electrons are suitable for clinical use.

Electrons↗
PubMed1995

Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control?

PURPOSE: To evaluate potential prognostic factors in the treatment of extremity soft tissue sarcomas that may influence local control, distant metastases, and overall survival. METHODS AND MATERIALS: Sixty-seven patients with extremity soft tissue sarcomas were treated with curative intent by limb-sparing surgery and postoperative radiation therapy at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania, between October 1970 and March 1991. Follow-up ranged from 4-218 months. The median external beam dose was 60.4 Gy. In 13 patients, interstitial brachytherapy was used as a component of treatment. RESULTS: The 5-year local control rate for all patients was 87%. The 5-year local control rate for patients who received < or = 62.5 Gy was 78% compared to 95% for patients who received > 62.5 Gy had larger tumors (p = 0.008) and a higher percentage of Grade 3 tumors and positive margins than patients who received < or = 62.5 Gy. The 5-year local control rate for patients with negative or close margins was 100% vs. 56% in patients with positive margins (p = 0.002). Cox proportional hazards regression analysis was performed using the following variables as covariates: tumor dose, overall treatment time, interval from surgery to initiation of radiation therapy, margin status, grade, and tumor size. Total dose (p = 0.04) and margin status (p = 0.02) were found to significantly influence local control. Only tumor size significantly influenced distant metastasis (p = 0.01) or survival (p = 0.03). CONCLUSION: Postoperative radiation therapy doses > 62.5 Gy were noted to significantly improve local control in patients with extremity soft tissue sarcomas. This is the first analysis in the literature to demonstrate the independent influence of total dose on local control of extremity soft tissue sarcomas treated with adjuvant postoperative irradiation.

Adolescent↗
PubMed1995

Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies.

PURPOSE: The incidence of adenocarcinoma of the esophagus is increasing, but the optimal treatment for this disease is unknown. We evaluated the efficacy of chemoradiation and chemoradiation followed by esophagectomy as treatment for adenocarcinoma of the esophagus in sequential prospective nonrandomized phase II studies. METHODS AND MATERIALS: Between May 1981 and June 1992, all previously untreated patients (N = 35) with potentially resectable adenocarcinoma of the esophagus (clinical Stage I or II) were treated with curative intent in sequential prospective Phase II studies. From May 1981 to August 1987, 11 patients (median age 66) were treated with concurrent chemotherapy [mitomycin C, and 5-fluorouracil (5-FU)] and radiotherapy to a median dose of 60 Gy (CRT group). From September 1987 to June 1992, 24 patients (median age 65) were treated with the same regimen of chemoradiation followed by planned esophagectomy (CRT+PE group). Of these, 12 patients (median age 62) actually underwent esophagectomy (CRT+E subgroup). RESULTS: The median overall survival was 19 months for the CRT group and 15 months for the CRT+PE group. For the CRT+E subgroup, the median overall survival was 33 months. The 3-year actuarial overall survival for the CRT and the CRT+PE groups were 36 and 28% (p = 0.949). The subset of patients treated with chemoradiation followed by esophagectomy had a 3-year actuarial overall survival of 33% (p = 0.274). The 3-year actuarial freedom from local failure rates were similar: 62% in the CRT group vs. 58% in the CRT+PE group. Of the 12 patients who underwent esophagectomy (CRT+E group), 9 (75%) were free of local failure. Four of 12 (33%) patients had no pathologic evidence of malignancy in their surgical specimen. Six of 11 patients (55%) in the CRT group were free of local failure at the time of analysis. Two of five patients in this group who had local recurrence at 2 and 10 months underwent surgical salvage with subsequent survivals of 20 and 100 months, respectively. Treatment-related mortality was 0 out of 11 in the CRT group and 2 out of 24 in the CRT+PE group. Dysphagia relief was similar in the CRT group vs. the CRT+E subgroup; however, a greater percentage of patients treated with chemoradiation alone had normal long-term swallowing function when compared to those patients also undergoing esophagectomy (100% vs. 73%). CONCLUSION: High-dose chemoradiation alone appears to provide similar survival and relief of dysphagia compared with high-dose chemoradiation followed by esophagectomy for patients with potentially resectable esophageal adenocarcinoma. Local failure may be higher in patients undergoing chemoradiation compared to chemoradiation followed by esophagectomy, but surgical salvage is possible, thus providing similar overall local control. However, because of the small number of patients in each group, these treatment modalities need to be further evaluated in a prospective randomized Phase III study.

Adenocarcinoma↗
PubMed1995

Late effects of hyperfractionated radiotherapy for advanced head and neck cancer: long-term follow-up results of RTOG 83-13.

PURPOSE: The objective of this study was to examine the incidence of late effects of hyperfractionated radiotherapy for head and neck cancer as a function of the dose delivered, as well as the daily interfraction interval. In addition, we wished to examine the influence of other prognostic factors including age, gender, primary site, T- and N-stage, and overall stage on the late effects of hyperfractionated radiotherapy. METHODS AND MATERIALS: Between 1983 and 1987, 479 patients with advanced head and neck cancer were entered on a Phase ILE/II dose escalation trial of hyperfractionated radiotherapy. They were randomly assigned to receive a dose of 67.2, 72.0, 76.8, or 81.6 Gy, delivered at 1.2 Gy/fraction, twice a day (BID), 5 days/week. Of the 451 analyzable patients, 399 patients who received > or = 64.8 Gy and had a follow-up > 90 days were eligible for this study. Acute and late effects were scored with the RTOG/EORTC late radiation morbidity scoring scheme. For this analysis, patients were subclassified by the actual doses delivered and by an average daily interfraction interval of < or = 4.5 h or > 4.5 h. The incidence of late effects was estimated using a cumulative incidence approach. RESULTS: Fifty-nine patients received 67.2 +/- 2.4 Gy, 119 received 72.0 +/- 2.4 Gy, 98 received 76.8 +/- 2.4 Gy, and 123 received 81.6 +/- 2.4 Gy. The proportion of patients treated with a daily interfraction interval of > 4.5 h was 32, 50, 43, and 71%, respectively. The four treatment groups were well balanced with respect to pretreatment characteristics. The median follow-up was 1.71 years (range: 0.24-9.6) for all evaluable patients and 6.12 years for 85 alive patients. There was no significant difference in the incidence of late effects between the different dose levels. At 5 years, the cumulative incidence of late effects was 17, 14, 20, and 13% for grade 3, and 7, 3, 7, and 5% for grade 4. However, the incidence of late effects differed significantly with respect to daily interfraction interval. The cumulative incidence of grade 4 late effects increased from 6.3% at 2 years to 7.5% at 3 years to 8.0% at 4 years and 8.6% at 5 years with an interval of < or = 4.5 h, while it remained at a constant of 2.0% with an interval of > 4.5 h during the same period (p = 0.0036). Multivariate analysis showed that among the prognostic factors examined, daily interfraction interval of < or = 4.5 h was the only significant independent prognostic factor for the development of grade 3+ or grade 4 late effects (p = 0.0167 and p = 0.0013, respectively). CONCLUSION: Results of this randomized Phase ILE/II trial of hyperfractionated radiotherapy in head and neck cancer showed no apparent dose-response relationship for late effects within the range of 67.2-81.6 Gy. Daily interfraction interval was a significant independent factor for the development of late effects in a multivariate analysis.

Adult↗
PubMed1995

Conformal treatment of prostate cancer with improved targeting: superior prostate-specific antigen response compared to standard treatment.

PURPOSE: Conformal radiation therapy (CRT) decreases the morbidity of prostate cancer treatment, but no published data attest to the improved ability of CRT to control disease. Therefore, we compared Prostate-Specific Antigen (PSA) response at 1 year among similarly staged patients treated by conformal techniques to those treated with conventional approaches, looking for an early indicator of tumor response. METHOD AND MATERIALS: Patients with locally advanced disease were treated by pelvic field followed by prostate field conedowns; those with early stage/low grade disease received only prostate field irradiation. Between October, 1987 and November, 1991, conventional treatments used rectangular beams with or without corner blocks. Neither urethrography nor immobilization casts were used for conventionally treated patients. Between April, 1989 and December, 1992, conformal treatments have used rigid immobilization and Computed Tomography-based, beams-eye-view field design. As such, our conformal approach allowed improved targeting. Median prescribed doses (minimal doses to the Planning Target Volume) were 70 Gy (66-73 Gy) and 70.2 Gy (64.8-75 Gy) for conventionally and conformally treated patients, respectively. Median daily fraction size was 1.8 Gy for conventional treatment and 2.0 Gy for conformal therapy. Baseline PSA data were available on 170 consecutive patients treated conformally and 90 consecutive patients treated conventionally. RESULTS: Among those receiving only prostatic field irradiation, 12-month PSA values returned to normal in 96% and 85% of conformally and conventionally treated patients, respectively, when normalization was defined as < or = 4 ng/ml (p < 0.03) and in 76% vs. 55% of patients when PSA normalization was defined as < or = 1.5 ng/ml (p < 0.02). Among those receiving pelvic irradiation prior to prostatic conedown, PSA normalization (< or = 4 ng/ml) occurred in 82% and 61% (p < 0.01) of conformally and conventionally treated patients, respectively, and in 56% vs. 38% of patients when normalization was defined as < or = 1.5 ng/ml (p < 0.05). In a multivariate analysis, pretreatment PSA level (< or = 15 vs. > 15), and the use of conformal irradiation were statistically significant prognostic discriminants of PSA normalization at 1 year while total irradiation dose, clinical stage, and the addition of pelvic fields were not significant. CONCLUSIONS: As measured by PSA normalization, conformal techniques with improved targeting produced responses that were significantly better than conventional techniques among patients treated with definitive irradiation. These results, coupled with our previously documented reduction of acute and chronic sequelae, support the continued use of CRT as a more effective method of treatment for prostate cancer.

Humans↗
PubMed1995

Radiation therapy quality control in a clinical trial of adjuvant postoperative treatment for rectal cancer.

PURPOSE: Deviations from protocol can detract from the reliability of results obtained in prospective clinical trials. In an effort to decrease the number of deviations in a prospective trial of adjuvant treatment for rectal cancer, we undertook pretreatment review of the irradiated fields. METHODS AND MATERIALS: Before initiation of radiation therapy, patients' radiation therapy fields were simulated by their radiation oncologists and films were submitted for review. The treating physicians were then informed whether their fields were in compliance with the protocol or whether any modifications were needed. RESULTS: Among the 625 patients participating in this study who received radiation therapy as a component of protocol treatment, 419 (67%) had no radiation therapy deviations, 127 (20%) had minor deviations, and 51 (8%) had major deviations; 28 (4%) could not be evaluated or did not receive protocol treatment because of circumstances beyond the treating radiation oncologist's control. The pretreatment quality control review identified major deviations in the radiation portals for 57 cases; these findings were communicated to the radiation oncologists prior to initiation of treatment, and, on final review, 40 had no deviation or only minor deviation. CONCLUSION: In the absence of pretreatment quality control review, 40 additional patients would have had major deviations from their radiation therapy protocol. On the basis of these findings, it is estimated that pretreatment quality control reduced the rate of major deviation from 15% to 8%. Pretreatment review of radiation therapy parameters is an effective method of reducing the frequency of major deviations in prospective clinical trials.

Clinical Protocols↗
PubMed1995

Late effects of radiation therapy on the gastrointestinal tract.

Late gastrointestinal complications of radiation therapy have been recognized but not extensively studied. In this paper, the late effects of radiation on three gastrointestinal sites, the esophagus, the stomach, and the bowel, are described. Esophageal dysmotility and benign stricture following esophageal irradiation are predominantly a result of damage to the esophageal wall, although mucosal ulcerations also may persist following high-dose radiation. The major late morbidity following gastric irradiation is gastric ulceration caused by mucosal destruction. Late radiation injury to the bowel, which may result in bleeding, frequency, fistula formation, and, particularly in small bowel, obstruction, is caused by damage to the entire thickness of the bowel wall, and predisposing factors have been identified. For each site a description of the pathogenesis, clinical findings, and present management is offered. Simple and reproducible endpoint scales for late toxicity measurement were developed and are presented for each of the three gastrointestinal organs. Factors important in analyzing late complications and future considerations in evaluation and management of radiation-related gastrointestinal injury are discussed.

Dose-Response Relationship, Radiation↗
PubMed1995

Transforming growth factor alpha expression as a potential survival prognosticator in patients with esophageal adenocarcinoma receiving high-dose radiation and chemotherapy.

PURPOSE: Transforming growth factor alpha (TGFA) stimulates the growth and proliferation of cells, and its overexpression has been correlated with patient survival in a variety of tumors, including squamous carcinoma of the esophagus. This study was performed to investigate the influence of TGFA in patients with esophageal adenocarcinoma (EA) receiving high-dose radiation and chemotherapy (HDRCT). METHODS AND MATERIALS: Thirty-one patients with localized esophageal adenocarcinoma were enrolled in a Phase II study involving high dose radiation and concurrent 5-fluorouracil (5-FU)/mitomycin-C with or without esophagectomy. Twenty-seven pretreatment (tumor not available in 4) and 11 posttreatment (insufficient tumor in 20) specimens were immunostained using the avidin-biotin-peroxidase technique. RESULTS: Fifteen of 27 (56%) pretreatment and 4 out of 11 (36%) postchemoradiation specimens had intense TGFA staining. Eight patients with intense and seven with little or no staining on pretreatment biopsy underwent esophagectomy. Median survival for the eight patients was 28 months, and for the seven patients 19 months (p = 0.4). Transforming growth factor alpha staining of posttreatment specimens that contained residual tumor also did not correlate with overall (p = 0.36) or disease-free (p = 0.17) survival. Among the 10 patients with both pre and posttreatment TGFA specimens, decreasing or negative TGFA expression was associated with a better median disease-free survival (32 vs. 13 months, p = 0.04) than persistently positive or increasing TGFA expression. CONCLUSION: There is frequent overexpression of TGFA in EA. Although pretreatment TGFA expression was not associated with survival, patients with tumors that persistently expressed or that increased TGFA expression had a worse prognosis. Posttreatment TGFA expression may serve as a prognostic marker in patients with EA treated with HDRCT.

Adenocarcinoma↗