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R J Myerson

Publications and source records attributed to R J Myerson.

At least 19 recordsLinked to original sources
PubMed2005

Experience with a small animal hyperthermia ultrasound system (SAHUS): report on 83 tumours.

An external local ultrasound (US) system was developed to induce controlled hyperthermia of subcutaneously implanted tumours in small animals (e.g., mice and rats). It was designed to be compatible with a small animal positron emission tomography scanner (microPET) to facilitate studies of hyperthermia-induced tumour re-oxygenation using a PET radiopharmaceutical, but it is applicable for any small animal study requiring controlled heating. The system consists of an acrylic applicator bed with up to four independent 5 MHz planar disc US transducers of 1 cm in diameter, a four-channel radiofrequency (RF) generator, a multiple thermocouple thermometry unit, and a personal computer with custom monitoring and controlling software. Although the system presented here was developed to target tumours of up to 1 cm in diameter, the applicator design allows for different piezoelectric transducers to be exchanged and operated within the 3.5-6.5 MHz band to target different tumour sizes. Temperature feedback control software was developed on the basis of a proportional-integral-derivative (PID) approach when the measured temperatures were within a selectable temperature band about the target temperature. Outside this band, an on/off control action was applied. Perfused tissue-mimicking phantom experiments were performed to determine optimum controller gain constants, which were later employed successfully in animal experiments. The performance of the SAHUS (small animal hyperthermia ultrasound system) was tested using several tumour types grown in thighs of female nude (nu/nu) mice. To date, the system has successfully treated 83 tumours to target temperatures in the range of 41-43 degrees C for periods of 65 min on average.

Algorithms↗
PubMed2004

MicroPET-compatible, small animal hyperthermia ultrasound system (SAHUS) for sustainable, collimated and controlled hyperthermia of subcutaneously implanted tumours.

An external ultrasound system was developed for the heating of subcutaneously implanted tumours in small animals. This small animal hyperthermia ultrasound system (SAHUS) was designed to be compatible with a microPET (small animal positron emission tomography) scanner to facilitate studies of hyperthermia effects on tumour hypoxia. Collimation and localization of energy deposition, a specific goal for the new device to avoid regional and/or systemic heating of small animals, was demonstrated using thermoradiography following high-power short-time heating of a layered gel phantom. The in vivo heating capabilities of the SAHUS were tested using PC3 cell line tumours (2000-2700 mm(3)) grown in the lateral proximal thighs of Nu-/Nu- nuBR nude mice. Intratumour temperatures were recorded during heating trials with deep and superficial interstitial thermocouples. The experimental data showed that the SAHUS could produce hyperthermia in 8 +/- 2 mm diameter tumours in small animals to a target temperature of 41.5 degrees C and maintain it within a narrow temperature range (+/- 0.3 degrees C) for up to 4 h without raising the core temperature of the animals. PET imaging studies, data to be published separately, were conducted before and during SAHUS-induced hyperthermia. Both devices performed as expected and there was no significant decrease in image quality. In this paper, the new SAHUS is described and data from phantom and in vivo experiments presented.

Acrylic Resins↗
PubMed2004

Modelling heat-induced radiosensitization: clinical implications.

Clinically achievable minimum tumour temperatures are in the order of about 41 degrees C. Therefore, it is important to evaluate mechanisms by which temperatures in this range might enhance cytotoxicity. Previous in vitro studies have demonstrated that 1-4 h (depending on the sequencing of modalities) of heating at 41 degrees C produces substantial heat-induced radiosensitization with little or no cell killing by heat alone. The increased radiation sensitivity is best modelled as a change in the single hit, alpha, parameter (with no significant effect on the two-hit parameter, beta) of the cell survival curve. The implications of heat-induced radiosensitization being mediated by a change in alpha on the traditional thermal enhancement ratio (for various radiation doses/fraction and alpha/beta) are reviewed. Response rates for a cohort of 60 patients enrolled on a prospective thermal dose escalation study are modelled assuming that the thermal dose dependence of heat-induced radiosensitization is modulated by a heat-induced delta alpha. The clinical data are fitted with delta alpha about 0.05-0.1 Gy-1. Randomized trials reported in the literature and the implication for the design of future prospective trials are reviewed in light of these observations.

Animals↗
PubMed2004

Transfection of human tumour cells with Mre11 siRNA and the increase in radiation sensitivity and the reduction in heat-induced radiosensitization.

Double-strand DNA breaks (DSBs) are potentially lethal DNA lesions induced by ionizing radiation. In eukaryotes, DSBs can be repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). DNA repair protein Mre11 participates in both the NHEJ and HR DNA repair pathways. Hyperthermia has been used clinically as a radiosensitizer. However, the mechanisms by which radiosensitization is induced by hyperthermia, especially moderate hyperthermia (41 degrees C) are not fully understood. Previous studies suggest that 41 degrees C reduces the nuclear Mre11 protein level in a manner that correlates with heat-induced changes in radiation sensitivity. Therefore, siRNA technology was used in the present study to reduce Mre11 gene expression to determine if reduced Mre11 protein levels induced radiosensitization and if such radiosensitization is similar to that induced by moderate hyperthermia. The results show that (1) the cellular level of the Mre11 protein was reduced about 60 +/- 18% by a 24-h treatment with siRNA. Results from the Mre11 protein turnover assay showed a half-life of 11.6 +/- 0.5 h for the Mre11 protein, which is consistent with reduction in protein level in 24 h after Mre11 siRNA treatment assuming a delay of 4-8 h to reduce RNA levels. After 48 h in siRNA, cellular Mre11 protein levels increased to approximately pretreatment levels. NSY cells were sensitized to ionizing radiation after 24 h of treatment with Mre11 siRNA. Two hours at 41 degrees C did not increase the radiation sensitivity of cells with a reduced Mre11 protein level following a 24-h siRNA treatment. These data support the conclusion that the DSB repair protein, Mre11, appears to be a target for radiosensitization by moderate hyperthermia.

Adenocarcinoma↗
PubMed2001

Treatment of rectal adenocarcinoma with endocavitary and external beam radiotherapy: results for 199 patients with localized tumors.

PURPOSE: Endocavitary radiation (RT) provides a conservative alternative to proctectomy. Although most suitable for small, mobile lesions, patients with less favorable tumors are often referred if they are poor surgical candidates. Knowing the extent to which radiation can control such tumors can be an important factor in making clinical decisions. METHODS AND MATERIALS: One hundred ninety-nine patients, who received endocavitary RT with or without external beam RT (EBRT) during 1981 through 1995, were followed for disease status for a median of 70 months, including deaths from intercurrent causes. In the early years of the study, 21 patients were treated with endocavitary RT alone, the remainder of the patients received pelvic EBRT (usually 45 Gy in 25 fractions) 5-7 weeks before endocavitary RT. RESULTS: Overall, 141 patients (71%) had local control with RT alone. Salvage surgery rendered an additional 20 patients disease free, for an ultimate local control rate of 81%. On multivariate analysis for local control (excluding surgical salvage), the most significant factors were mobility to palpation, use of EBRT, and whether pretreatment debulking of all macroscopic disease had been done (generally a piecemeal, nontransmural procedure). Of 77 cases staged by transrectal ultrasonography, the local control rate with RT alone was 100% for uT1 lesions, 85% (90% with no evidence of disease after salvage) for freely mobile uT2 lesions, and 56% (67% with no evidence of disease after salvage) for uT3 lesions and uT2 lesions that were not freely mobile. CONCLUSIONS: Patients with small mobile tumors that are either uT1 or have only a scar after debulking achieve excellent local control with endocavitary RT. About 15% of mobile uT2 tumors fail RT; therefore, careful follow-up is critical. Small uT3 tumors are appropriate for this treatment only if substantial contraindications to proctectomy are present.

Adenocarcinoma↗
PubMed2001

A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.

BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02). There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

Adenocarcinoma↗
PubMed2001

Pretreatment clinical findings predict outcome for patients receiving preoperative radiation for rectal cancer.

BACKGROUND: As a sole modality, preoperative radiation for rectal carcinoma achieves a local control comparable to that of postoperative radiation plus chemotherapy. Although the addition of chemotherapy to preoperative treatment improves the pathologic complete response rate, there is also a substantial increase in acute and perioperative morbidity. Identification of subsets of patients who are at low or high risk for recurrence can help to optimize treatment. METHODS: During the period 1977-95, 384 patients received preoperative radiation therapy for localized adenocarcinoma of the rectum. Ages ranged from 19 to 97 years (mean 64.4), and there were 171 females. Preoperative treatment consisted of conventionally fractionated radiation to 3600-5040 cGy (median 4500 cGy) 6-8 weeks before surgery in 293 cases or low doses of <3000 cGy (median 2000 cGy) immediately before surgery in 91 cases. Concurrent preoperative chemotherapy was given to only 14 cases in this study period. Postoperative chemotherapy was delivered to 55 cases. RESULTS: Overall 93 patients have experienced recurrence (including 36 local failures). Local failures were scored if they occurred at any time, not just as first site of failure. For the group as a whole, the actuarial (Kaplan-Meier) freedom from relapse (FFR) and local control (LC) were 74% and 90% respectively at 5 years. Univariate analysis of clinical characteristics demonstrated a significant (p < 0.05) adverse effect on both LC and FFR for the following four clinical factors: (1) location <5 cm from the verge, (2) circumferential lesion, (3) near obstruction, (4) tethered or fixed tumor. Size, grade, age, gender, ultrasound stage, CEA, radiation dose, and the use of chemotherapy were not associated with outcome. Background of the surgeon was significantly associated with outcome, colorectal specialists achieving better results than nonspecialist surgeons. We assigned a clinical score of 0 to 2 on the basis of how many of the above four adverse clinical factors were present: 0 for none, 1 for one or two, 2 for three or four. This sorted outcome highly significantly (p < or = 0.002, Tarone Ware), with 5-year LC/FFR of 98%/85% (score 0), 90%/72% (score 1), and 74%/58% (score 2). The scoring system sorts the data for both subgroups of surgeons; however, there are substantial differences in LC on the basis of the surgeon's experience. For colorectal specialists (251 cases), the 5-year LC is 100%, 94%, and 78% for scores of 0, 1, and 2, respectively (p = 0.004). For the more mixed group of nonspecialist surgeons (133 cases), LC is 98%, 80%, and 65% for scores of 0, 1, and 2 (p = 0.008). In multivariate analysis, the clinical score and surgeon's background retained independent predictive value, even when pathologic stage was included. CONCLUSIONS: For many patients with rectal cancer, adjuvant treatment can be administered in a well-tolerated sequential fashion-moderate doses of preoperative radiation followed by surgery followed by postoperative chemotherapy to address the risk of occult metastatic disease. A clinical scoring system has been presented here that would suggest that the local control is excellent for lesions with a score of 0 or (if the surgeon is experienced) 1, and therefore sequential treatment could be considered. Cases with a clinical score of 2 should be strongly considered for protocols evaluating more aggressive preoperative treatment, such as combined modality preoperative treatment.

Adenocarcinoma↗
PubMed2001

Neoadjuvant therapy for adenocarcinoma of the rectum: tumor response and acute toxicity.

PURPOSE: This study was designed to evaluate the down-staging effect and acute toxicity of preoperative radiation and chemoradiation for primary adenocarcinoma of the rectum. METHODS: The results of pretreatment staging with transrectal ultrasound and computed tomography were compared with final histologic stage in 260 consecutive patients who underwent neoadjuvant therapy and proctectomy for primary adenocarcinoma of the rectum. Patients underwent short-course radiation (2,000 cGy in five fractions), long-course radiation (4,500 cGy in 25 fractions), or chemoradiation (4,500 cGy in 25 fractions with concurrent chemotherapy). RESULTS: Down-staging of one or more T stages occurred in 116 of 260 (45 percent) patients overall (short-course radiation 34/82 (42 percent), long-course radiation 55/122 (45 percent), chemoradiation 27/56 (48 percent), P = not significant). Down-staging of one or more N stages occurred in 85 of 178 (48 percent) patients overall (short-course radiation 12/45 (27 percent), long-course radiation 49/86 (57 percent), chemoradiation 24/47 (51 percent), P = 0.003). Complete pathologic response was observed in 16 of 260 (6 percent) patients overall (short-course radiation 4/82 (5 percent), long-course radiation 5/122 (4 percent), chemoradiation 7/56 (13 percent), P = 0.08). Resection with negative margins (distal, proximal, and radial) was achieved in 211 of 227 patients (93 percent) in whom complete radial margin data were available. Permanent stomas were created in 35 percent of patients; temporary stomas were created in 15 percent. Thirty-three Grade 3 or 4 toxicities occurred in 22 of 260 (8 percent) patients overall during neoadjuvant therapy. Toxicity was more frequent in patients receiving chemoradiation (14/56; 25 percent) and long-course radiation (8/122; 7 percent) than in those receiving short-course radiation (0/82; 0 percent), P < 0.0001. Perioperative complications occurred in 93 patients overall (36 percent). The postoperative mortality rate was 0.4 percent (1/260). There was no significant difference in the complication rate between patients treated with short-course radiation (26/82; 32 percent), long-course radiation (46/122; 36 percent), and chemoradiation (21/56; 38 percent). CONCLUSION: Neoadjuvant therapy for adenocarcinoma of the rectum is well tolerated and can produce substantial down-staging and a high curative resection rate. Chemoradiation can achieve high complete pathologic response rates, although toxicity during neoadjuvant therapy is greater than for radiation alone. Short-course radiation can achieve down-staging of both T stage and N stage.

Adenocarcinoma↗
PubMed2001

Neoadjuvant external beam radiation and proctectomy for adenocarcinoma of the rectum.

PURPOSE: The aim of this study was to determine the survival rate, local failure, and perioperative morbidity in patients with adenocarcinoma of the rectum undergoing curative proctectomy who were felt to have transmural disease on preoperative assessment. Eighty-nine percent of these patients were treated with preoperative external beam radiotherapy. METHODS: The records of 191 consecutive patients undergoing abdominal surgical procedures for primary treatment of rectal cancer were reviewed. The product-limit method (Kaplan-Meier) was used to analyze survival rate and tumor recurrence. RESULTS: One patient was excluded from survival analysis because of incomplete record of tumor stage. The study population comprised 109 males and 81 females, median age 64 (range, 33-91) years. Curative resection was performed in 152 of these 190 patients (80 percent), including low anterior resection with coloproctostomy or coloanal anastomosis (n = 103), abdominoperineal resection (n = 44), Hartmann's procedure (n = 4), and pelvic exenteration (n = 1). Mean follow-up of patients undergoing curative resection was 96 +/- 48 months. Palliative procedures were performed in 38 of 190 patients (20 percent). Perioperative mortality was 0.5 percent (1/190). Complications occurred in 64 patients (34 percent). The anastomotic leak rate was 4 percent (5/128). Disease-free five-year survival rate by pathologic stage was as follows: Stage I, 90 percent; Stage II, 85 percent; Stage III, 54 percent; Stage IV, 0 percent; and no residual tumor, 90 percent. Of the 152 patients treated with curative resection, disease-free survival rate was 80 percent at five years. Preoperative external beam radiation was administered to 135 of these 152 patients (89 percent). Tumor recurred in 32 of 152 patients (21 percent) treated with curative resection. The predominant pattern of recurrence was distant failure only. Kaplan-Meier overall local recurrence (local and local plus distant) at five years was 6.6 percent. The local recurrence rate paralleled tumor stage: Stage I, 0 percent; Stage II, 6 percent; Stage III, 20 percent; and no residual tumor, 0 percent. CONCLUSION: Preoperative external beam radiotherapy and attention to mesorectal dissection can achieve low local recurrence and excellent long-term survival rate in patients with adenocarcinoma of the rectum. Moreover, these goals can be obtained with low morbidity and mortality.

Adenocarcinoma↗
PubMed2001

Radiation therapy for epidermoid carcinoma of the anal canal, clinical and treatment factors associated with outcome.

BACKGROUND AND PURPOSE: In recent years, treatment with combined chemotherapy and radiation has become the standard of care for epidermoid carcinoma of the anus. However, optimal radiotherapy techniques and doses are not well established. MATERIALS AND METHODS: During the period 1975-1997, 106 patients with epidermoid carcinoma of the anal canal underwent radiation therapy. Treatment policies evolved from radiation therapy alone or with surgery, to combined chemotherapy and radiation followed by surgery, to combined chemotherapy and radiation. RESULTS: Overall 74% of patients were NED (no evidence of disease) at last follow-up. The most important clinical correlate with ultimate freedom from disease (includes the contribution of salvage surgery) was extent of disease. The 5-year ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15% salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001, Tarone-Ware). There was no difference between planned vs. expectant surgery (5-year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The most important correlate with late toxicity was a history of major pelvic surgery (surgical vs. non-surgical group: P=0.013, Fisher's exact test, two-tailed summation). Thirty-three additional malignancies have been seen in 26 patients. The most common additional malignancies were gynecologic (nine cases), head and neck (six cases), and lung cancer (five cases). CONCLUSIONS: For T1/T2N0 disease, moderate doses of radiation combined with chemotherapy provided adequate treatment. T4N0 and N+ lesions are the most appropriate candidates for investigational protocols evaluating dose intensification. T3N0 tumors may also be appropriate for investigation; however, dose intensification may ultimately prove counterproductive if the cure rate is not improved and salvage surgery is rendered more difficult. The volume of irradiated small bowel should be minimized for patients who have a past history of major pelvic surgery or who (because of locally advanced tumors) may need salvage surgery in the future. Because of the occurrence of additional malignancy, patients with anal cancer should receive general oncologic screening in long-term follow-up.

Anus Neoplasms↗
PubMed2000

Outcome of patients with rectal adenocarcinoma and localized pelvic non-nodal metastatic foci.

PURPOSE: The aim of this study was to evaluate the outcome of patients with primary rectal adenocarcinoma and soft tissue metastatic foci restricted to the pelvis and to determine whether this entity, which is considered N1 disease in the American Joint Committee on Cancer staging system, behaves like completely replaced nodal disease or the first sign of M1 disease. The clinical course for patients with this finding is not well-described in the literature. METHODS: The authors retrospectively reviewed the medical records of 395 patients with rectal adenocarcinoma who received radiation treatment. Eighteen patients had pelvic soft tissue metastatic foci. Exclusions from this study included 1) cases without metastatic pelvic foci; 2) cases of recurrent cancer; 3) cases with known distant metastatic disease as defined by American Joint Committee on Cancer criteria; and 4) cases with extrapelvic metastatic foci. All patients received adjuvant radiotherapy. Thirteen cases received preoperative radiotherapy. Four cases received postoperative radiotherapy. One case received both preoperative and postoperative radiotherapy. Eight cases received chemotherapy. RESULTS: All eighteen patients had T3 or T4 lesions. Thirteen patients had lymph nodes that contained metastatic disease and would therefore have been scored N1 or N2 even without the pelvic tumor implants. Sixteen of 18 (89 percent) patients died of disease after a survival time of 12 to 37 (mean, 25) months. Only 1 of 18 (6 percent) patients was disease free at five years. The other remaining survivor was undergoing palliative therapy for metastatic disease to the lung. This is significantly worse than our institution's experience with T3,4N+ disease after preoperative radiation (5-year survival, 11 vs. 56 percent; P = 0.0002, Generalized Wilcoxon of Breslow). There was a high incidence of local (9/18) and distant (14/18) failure. No other factor, including radiation dose, margin status, chemotherapy, T stage, and number of involved nodes or soft tissue implants, correlated independently with outcome. CONCLUSIONS: Pelvic metastatic foci confer a significantly worse prognosis than other T3,4N+ disease. Such cases should be excluded from prospective trials for localized disease. Although this entity probably represents M1 disease for most patients, survival can be long, and aggressive locoregional and systemic treatment is warranted.

Adenocarcinoma↗
PubMed1999

Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment.

BACKGROUND: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen. METHODS AND MATERIALS: During the period of 1975-1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%). RESULTS: With a post treatment follow-up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery). CONCLUSION: Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.

Adult↗
PubMed1999

Selection criteria for treatment of rectal cancer with combined external and endocavitary radiation.

PURPOSE: The aim of this study was to identify factors predictive of recurrence of rectal tumors treated with combined external and endocavitary radiation. METHODS: Seventy-two patients with rectal cancer were evaluated clinically and with transrectal ultrasound before combined external and endocavitary radiation. Ideal lesions were moderately differentiated, mobile, not ulcerated, <3 cm in diameter, and <12 cm from the anal verge. External radiation (4,500 cGy) was given during five weeks followed by endocavitary radiation (3,000 cGy x 2). Median follow-up was 31 (range, 7-93) months. RESULTS: Pretreatment transrectal ultrasound stages were uT1 (6 patients), uT2 (27 patients), and uT3 (39 patients). Clinical evaluation identified 26 ideal and 46 nonideal tumors. Overall recurrence was 36 percent; mean time to recurrence was 12 months. Ideal lesions recurred less than nonideal (15 vs. 48 percent; P = 0.01). Mobile lesions recurred less than tethered lesions (26 vs. 52 percent; P = 0.048). Transrectal ultrasound stage was predictive of recurrence (0 percent uT1, 22 percent uT2, and 51 percent uT3; P = 0.015). Surgery was possible in 14 of 17 patients with pelvic recurrence only; 11 patients (65 percent) had curative surgery. Distant metastases occurred in nine patients; all had pelvic recurrences, and six died of disease. CONCLUSION: Patients with uT3 or nonideal rectal cancers should not be offered combined external and endocavitary radiation for cure. Transrectal ultrasound stage is the only independent predictor of recurrence.

Adenocarcinoma↗
PubMed1998

Superficial hyperthermia and irradiation for recurrent breast carcinoma of the chest wall: prognostic factors in 196 tumors.

PURPOSE: To correlate patient-, tumor-, and treatment-related factors with subsequent local tumor control. METHODS AND MATERIALS: From 1977 to 1990, 196 subcutaneous/superficial lesions (179 measurable, 17 microscopic) in 151 patients with recurrent breast carcinoma of the chest wall were treated with superficial 915-MHz microwave hyperthermia and irradiation. The definition of min t43 > or = 10 min is that all monitored tumor catheters had a minimum of 1 hyperthermia session with temperatures > 43 degrees C for at least 10 min. RESULTS: Factors correlating with local control on univariate analysis included length of survival (> or = 1 year vs. < 1 year) (p < 0.0001), specific absorption rate (SAR) (> or = 25% vs. < 25%) (p = 0.0001), minimum t43 > 10 min (p < 0.0001), tumor volume (p < 0.0001), tumor surface area (p < 0.0001), tumor depth (p = 0.0002), number of hyperthermia sessions (p = 0.0003), and current radiation dose (p = 0.0012). On multivariate analysis, the factors best correlated with ultimate local control were SAR (p < 0.001) and number of hyperthermia sessions (p = 0.003). CONCLUSIONS: Multivariate analysis supports the importance of adequate specific absorption rate (SAR) coverage as a better predictor of local control than tumor volume, surface area, or depth. The explanation is that SAR can be correlated with the tumor surface area and depth, depending on the hyperthermia applicator characteristics. It is recommended that future clinical trials stratify study lesions into either SAR > or = 25% or < 25% because this can be readily estimated prior to initiating treatment. It is also recommended that future clinical trials attempt to have adequate lengths of follow-up after therapy to assess the results in long-term survivors.

Adult↗
PubMed1997

The National Cancer Data Base report on carcinoma of the anus.

BACKGROUND: The last 15 years have seen substantial advances in the management of anal carcinoma, primarily in the use of radiochemotherapy as definitive or adjuvant treatment. This study reviews the patterns of presentation, care, and outcome reflected in data from the National Cancer Data Base representing a broad range of medical centers. METHODS: Data on patients with anal carcinoma (on 1050 patients from 1988 and 1289 patients from 1993) were reviewed for patterns of care and presentation. The 1988 cases were also reviewed for outcome data. RESULTS: There was an increase in the use of chemotherapy between 1988 and 1993 (from 61.6% to 67.2%), and substantial differences were observed in the management of epidermoid carcinomas and adenocarcinomas. The majority of epidermoid carcinomas were managed nonsurgically, principally with combined chemotherapy and radiation, whereas three-fourths of patients with adenocarcinoma underwent surgery. The most important factors for favorable 5-year survival were early stage (ranging from 71.3% for Stage I to 23.1% for Stage IV), epidermoid carcinoma histology (57.6%, compared with 41.3% for adenocarcinoma), and female gender (56.2%, compared with 49.6% for males). For Stage I-II epidermoid carcinomas, the 5-year survival for patients who received nonsurgical treatment with radiochemotherapy was equivalent to that of patients who received surgical treatment (64.0% and 65.4%, respectively). CONCLUSIONS: This study confirms a trend in patterns of care favoring nonsurgical management with radiochemotherapy for epidermoid carcinomas of the anus. For adenocarcinomas, there has been a trend toward increasing use of multimodality therapy with surgery and adjuvant radiochemotherapy. Survival data from the 1988 cases confirmed the efficacy of conservative treatment with radiation plus chemotherapy for epidermoid carcinomas.

Adult↗
PubMed1996

An ultrasound system for simultaneous ultrasound hyperthermia and photon beam irradiation.

PURPOSE: An existing ultrasound system has been adapted for simultaneous use with external photon beam irradiation. The system is being used to investigate the potential for increased biological benefit of simultaneously combined hyperthermia and external beam irradiation with currently achievable temperature distributions. METHODS AND MATERIALS: An existing clinical ultrasound system has been modified for simultaneous operation with a 60Co teletherapy machine. The generator, thermometry system, computer, and applicators are located inside the treatment room, while the monitor and system control are located at the control console. Two approaches have been used clinically to combine the two modalities. In the first approach, an en-face setup is used in which the ultrasound beam and the photon beam travel through the same window of entry to the tumor. This is acheived by a reflecting system designed to deflect the ultrasound to the tumor while positioning the ultrasound transducer outside the radiation beam. The reflecting system consists of water and water-equivalent materials except for a 1 mm sheet of polished brass that is used as the reflector. The relative pressure fields were measured in water at the same distance from the ultrasound source using a scanning hydrophone with and without the reflector at the two operating frequencies of the device (1.0 and 3.4 MHz) for two applicators. Radiation dosimetry measurements were performed to determine the relationship between 60Co irradiation through the reflector and absorbed dose. In the second approach the ultrasound and the radiation beam travel into the tumor from different windows of entry such that the radiation beam passes through no portion of the water bolus prior to entering the patient. We have termed this approach the orthogonal approach. For both approaches, the radiation fraction is given in the middle of an uninterrupted 60-min hyperthermia treatment. RESULTS: The system modifications did not impair the ability to effectively deliver ultrasound hyperthermia or 60Co teletherapy. With the en-face approach the ultrasonic patterns generated with and without the reflector demonstrated that the ultrasound system maintained both a uniform and controllable heating pattern. The 60Co beam had no effect on the performance of the thermocouple thermometers. The radiation beam is attenuated nearly uniformly by the reflector system. To date, 10 patients have been treated with the en-face approach and 12 have been treated with the orthogonal approach (90 treatments). CONCLUSIONS: The clinical implementation of ultrasound hyperthermia simultaneous with 60Co irradiation is technically and clinically feasible without any complications or hazards to the patient. The implementation of a reflecting device allows en-face delivery of both the ultrasound and 60Co irradiation. Temperatures obtained during simultaneous treatments are comparable to those historically obtained during sequential treatments with the same commercial ultrasound device.

Calorimetry↗
PubMed1996

Design and dosimetric characteristics of a high dose rate remotely afterloaded endocavitary applicator system.

PURPOSE: An applicator is described for endocavitary treatment of rectal cancers using a high dose rate (HDR) remote afterloading system with a single high-intensity 192Ir source as an alternative to the 50 kVp x-ray therapy contact unit most frequently used in this application. METHODS AND MATERIALS: The applicator consists of a tungsten-alloy collimator with a 45 degree beveled end, placed in a protoscope with an elliptical cross-section. The resultant 3 cm diameter circular treatment aperture, located in the beveled face of the proctoscope, is irradiated by circular array of dwell positions located about 6.5 mm from the applicator surface. This beveled end allows patients with posterior wall tumors to be treated in the dorsal lithotomy position. The dose-rate distributions about the applicator were determined using a combination of thermoluminescent dosimetry (TLD-100 detectors) and radiochromic film dose measurement techniques along with Monte Carlo dosimetry calculations. TLD-100 (3 x 3 x 0.9 mm3 chips) measurements were used to measure the distribution of dose over the proctoscope surface as well as the central axis dose-rate distribution. Relative radiochromic film measurements were used to measure off-axis ratios (flatness and penumbra width) within the treatment aperture. These data were combined with Monte Carlo simulation results to obtain the final dose distribution. RESULTS: The tungsten collimator successfully limits the dose to the tissue in contact with the proctoscope walls to less than 12% of the prescribed dose. These results indicate that the HDR applicator system has slightly more penetrating depth-dose characteristics than the most widely used contact therapy x-ray machine. Flatness characteristics of the two treatment delivery systems are comparable, although the HDR endocavitary applicator has a significantly wider penumbra. Finally, the HDR applicator has a lower surface dose rate (1.5-4 Gy/min of dwell time) compared to 9-10 Gy/min for the x-ray unit. CONCLUSIONS: An applicator system has been developed for endocavitary treatment of early stage rectal carcinoma that uses a single-stepping source HDR remote afterloading system as a radiation source. The advantages of the HDR-based system over x-ray therapy contact units currently used in this clinical application are (a) enhanced flexibility in applicator design and (b) widespread availability of single-stepping source HDR remote afterloading systems.

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