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Biomedical subjects

L R Coia

Publications and source records attributed to L R Coia.

At least 55 records · Page 3Linked to original sources
PubMed1995

Management of retroperitoneal sarcomas: does dose escalation impact on locoregional control?

PURPOSE: Only 50% of patients with retroperitoneal sarcomas undergo complete resection and of these, 47% develop local tumor recurrence. To determine whether irradiation with dose escalation improves locoregional control, we reviewed the experience with adjuvant radiotherapy in the treatment of retroperitoneal sarcomas at the Fox Chase Cancer Center and the Hospital of the University of Pennsylvania. METHODS AND MATERIALS: Twenty-one patients with retroperitoneal sarcomas were treated with curative intent with surgical resection and radiation therapy at Fox Chase Cancer Center or the Hospital of the University of Pennsylvania between May 1965 and July 1992. Follow-up ranged from 14-340 months. Nineteen patients were treated postoperatively and 2 preoperatively. Radiation doses were between 36.0 Gy and 90.0 Gy (median 54.0 Gy). RESULTS: The 2-year rates of local control and survival were 72% and 69%, respectively. Tumor size, stage, grade, and histology did not influence local control. Two of eight patients (25%) who received a total dose of > 55.2 Gy experienced local failure compared to 5 of 13 (38%) who received < or = 55.2 Gy. One patient experienced a small bowel obstruction that required surgical intervention. There were no other severe complications. CONCLUSION: Postoperative treatment with radiotherapy using a dose > 55.0 Gy is recommended for patients with retroperitoneal sarcomas following surgical resection due to the significant likelihood of local recurrence. Innovative adjuvant radiation techniques to escalate doses to greater than 55.0 Gy including intraoperative radiation therapy, brachytherapy, or use of small bowel exclusion devices to reduce small bowel toxicity should be considered for retroperitoneal sarcomas.

Adult↗
PubMed1995

Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation.

Malignant pleural mesothelioma (MPM) is a generally fatal disease with no standard treatment. There are encouraging reports using intraperitoneal chemotherapy to treat peritoneal mesotheliomas and intrapleural chemotherapy (IPC) to treat malignant pleural effusions. Our objective was to evaluate the efficacy of IPC after subtotal pleurectomy. Between 1988 and 1992, 20 consecutive patients with diffuse MPM limited to one hemithorax underwent subtotal pleurectomy. Thirteen patients with biopsy-proven MPM known prior to thoracotomy were enrolled in a phase II combined modality protocol consisting of perioperative intrapleural cisplatin (100 mg/m2) and ara-C (1,200 mg) after subtotal pleurectomy, followed by systemic cisplatin (50 mg/m2/week x 8) and mitomycin-C (8 mg/m2, days 1 and 36). Seven patients with MPM could not be enrolled because their diagnosis was made post-thoracotomy. These patients underwent subtotal pleurectomy with (n = 4) or without (n = 3) adjuvant radiation (4,500-5,000 cGy in 3 patients, 2,100 cGy in 1 patient). One of three patients who developed chemotherapy-related nephrotoxicity died, the only treatment-related mortality. All 3 patients requiring postoperative readmission received IPC. Significant morbidity did not occur in patients not receiving chemotherapy. Median survival and time to progression were significantly longer in patients not receiving IPC (21 vs. 9 months, P = 0.04; 12 vs. 6 months, P = 0.01). In conclusion, intrapleural and postoperative systemic chemotherapy resulted in significant toxicity and did not improve survival in our patients who underwent subtotal pleurectomy for MPM.

Aged↗
PubMed1995

Long-term follow-up of local excision and radiation therapy for invasive rectal cancer.

PURPOSE: Little is known regarding the long-term outcome of patients with rectal cancer treated by local excision and radiation therapy. We updated our institutional experience with this approach. METHODS: From January 1986 to December 1991, 23 patients (median age, 64 (range, 30-80) years) with mobile, moderately differentiated adenocarcinoma of the rectum were offered transanal excision. Two patients with large T3 tumors, who were judged intraoperatively to be unsuited for a local procedure, received radical resection and were excluded from analysis. Twenty-one patients underwent transanal excision en bloc (14) or piece-meal (7) through a resectoscope. Seven patients (74 percent) had either extensive medical problems or refused a colostomy. Patients received a median of 5,040 cGy postoperatively, and 15 also received 500 cGy preoperatively on protocol. Two patients received concomitant chemotherapy. Median follow-up is 56 months for all patients and 67 months for survivors (range, 27-92 months). RESULTS: There were 2 T1, 15 T2, and 4 T3 tumors. The distance from the anal verge was a median of 4 (range, 1-7) cm. The median tumor size was 3 (range, 2-7) cm. Sixteen patients had more than one-third of the wall involved. Four patients (19 percent) developed a local recurrence at 26, 30, 33, and 48 (median, 31.5) months. Three were salvaged (abdominoperineal resection = 2; low anterior resection = 1) and remain disease-free 18, 36, and 37 months postoperatively. Four patients (19 percent) developed metastases (lung = 3; liver = 1) at 3, 22, 25 and 44 months after initial treatment (median, 23.5 months). The actuarial five-year overall, disease-free and recurrence-free survival are 77, 75, and 58 percent, respectively. Twelve patients (57 percent) have no evidence of disease while retaining their rectum. There was one postoperative death. CONCLUSIONS: Long-term follow-up confirms that local excision and radiation therapy is of value in patients with mobile tumors of the rectum. It suggests that this treatment can be offered to those patients who refuse a colostomy or are medically compromised and may be an acceptable option for selected patients with T2 or T3, mobile adenocarcinomas of the rectum.

Adenocarcinoma↗
PubMed1995

Use of multiplanar reformatted radiographic and digitally reconstructed radiographic images for planning conformal radiation therapy.

A three-dimensional treatment planning system capable of gantry, collimator, and table rotations is required for a noncoplanar conformal therapy. Unfortunately, such a system is not widely available. A method in which multiplanar reformatted radiographic (MPR) and digitally reconstructed radiographic (DRR) images are used is presented for conformal treatment of brain tumors. A head phantom containing a target volume was scanned on a computed tomographic (CT) simulator. The coronal MPR images were digitized on a treatment planning system to create a conformal block of the planned treatment field. The DRR images were generated on the CT simulator with the setup parameters calculated from the treatment planning system. A second set of conformal blocks was generated based on DRR images of the fields. The accuracy of the MPR- and DRR-generated blocks was verified on the vertex field. The differences between the actual planning target volume and the field edges of the MPR and DRR blocks were within +/- 4 mm and +/- 2 mm, respectively. The authors conclude that the MPR and DRR images could be successfully used to generate conformal blocks and for treatment planning of noncoplanar beams in radiation therapy.

Brain Neoplasms↗
PubMed1995

Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx.

PURPOSE: A number of reports have documented the relationship between pretreatment hemoglobin level and local control and/or survival in the treatment of cervix, bladder, and advanced head and neck tumors. Consideration of correcting anemia before initiation of radiation therapy may prove increasingly important as clinical trials use intensive induction chemotherapy in the treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce anemia, which in turn may reduce the effectiveness of subsequent irradiation. MATERIALS AND METHODS: One hundred nine patients with T1-2N0 squamous cell carcinoma of the glottic larynx were treated with definitive radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times ranged from 26 to 165 months (median, 82). RESULTS: The 2-year local control rate for patients who presented with a hemoglobin level < or = 13 g/dL was 66%, compared with 95% for patients with a hemoglobin level more than 13 g/dL (P = .0018). The 2-year survival rate for patients with a hemoglobin level < or = 13 g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13 g/dL (P < .001). Cox proportional hazards regression analysis showed that hemoglobin level (P = .0016) was the only variable that significantly influenced local control (P = .0016) and survival (P < .0001). CONCLUSION: Patients who presented with hemoglobin levels more than 13 g/dL had significantly higher local control and survival rates. The strong apparent correlation between hemoglobin level, local control, and survival supports consideration of correcting anemia before initiation of radiation therapy.

Actuarial Analysis↗
PubMed1994

Radiation treatment decreases transforming growth factor alpha expression in squamous carcinoma of the tongue.

Ionizing radiation (XRT) is often used to treat squamous cell carcinoma of the tongue (SCCT) but little is known of its genetic effects on surviving cancer cells. The effect of XRT on p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha (TGF alpha) tumor marker expression was evaluated using immunohistochemical analysis in 79 patients with SCCT. Sixty-six patients received no radiation, while 13 received XRT before surgery. Radiation did not influence EGFR or p53 expression. TGF alpha expression, however, was significantly decreased in radiated tumors (15% versus 43%, P = 0.04). These data suggest that XRT either decreases the expression of TGF alpha in SCCT (suggesting a genetic alteration in surviving cancer cells), or does not kill cancer cells with decreased TGF alpha expression. In the latter case, diminished TGF alpha expression may serve as a marker of radioresistance.

Aged↗
PubMed1994

Preoperative high-dose radiation and chemotherapy in adenocarcinoma of the esophagus and esophagogastric junction.

BACKGROUND: Esophageal adenocarcinoma (EA) incidence is rising. Defining optimal management is essential because median survival after surgery alone is only approximately 12 months. High-dose radiation (> 5000 cGy) and chemotherapy (HDRCT) preoperatively for patients with EA has not been fully investigated. We evaluated tumor response, resectability, and survival following HDRCT in patients with localized EA. METHODS: Thirty patients with American Joint Committee on Cancer (AJCC) clinical stage I or II EA were prospectively treated with HDRCT. The treatment consisted of 60 Gy radiation at 2 Gy per fraction with concurrent infusional 5-fluorouracil (5-FU) and a bolus of mitomycin C followed by esophagogastrectomy. The range of follow-up was 7 to 69 months, with a median of 31 months. RESULTS: Twenty of 30 patients (67%) received full-course HDRCT. Severe esophagitis precluded full-dose radiation in 10 patients. Three patients developed neutropenia and fever requiring admission to a hospital. Two patients died preoperatively of treatment-related complications. Nine patients were not explored. Eighteen patients were resected with curative intent; the remaining three had metastatic disease at laparotomy. Seven of 18 resected patients (39%), or 7/30 (23%) of all patients treated, had a pathologic complete response. There was one operative death. Overall local control was seen in 25/30 patients (83%). Median overall survivals for resected and for all patients were 23 and 13 months, respectively. CONCLUSIONS: Preoperative HDRCT in patients with EA results in encouraging local tumor response and local control. Overall survival, however, may not be improved, and the treatment-related mortality of 10% is higher than reported with surgery alone or with preoperative chemotherapy.

Adenocarcinoma↗
PubMed1993

Limb-preserving treatment for soft tissue sarcomas of the extremities. The significance of surgical margins.

BACKGROUND AND METHODS: Between 1970 and 1990, 74 patients with extremity soft tissue sarcomas began a regimen of limb-sparing surgery and irradiation. Ninety-two percent received postoperative irradiation, 7% received preoperative irradiation, and one patient was treated with radiation after an incisional biopsy only. Radiation was administered with a shrinking-field technique (median total dose, 63 Gy; range, 39.6-71 Gy), with 14 patients receiving interstitial brachytherapy as a component of treatment. Ten patients received adjuvant chemotherapy. RESULTS: Local control of disease was 82% at 5 years, and 95% after salvage therapy. The actuarial risk of distant disease recurrence was 27%, with an overall survival rate of 70% at 5 years. Histologic subtype, tumor grade, size of tumor, location of tumor, status of the surgical margins, use of chemotherapy, radiation dose, interval until initiation of radiation therapy, and use of a brachytherapy boost were analyzed to determine their effect on survival, local control, and freedom from distant metastasis. Microscopic involvement of the surgical margins predicted for local disease recurrence (P = 0.0002), distant disease recurrence (P = 0.008), and poorer overall survival (P = 0.02). Low histologic grade was favorably correlated with freedom from distant disease recurrence (P = 0.004) and survival (P = 0.002). Patients with liposarcomas had superior local control (P = 0.004) compared with patients with tumors of other histologic subtypes. Five patients experienced a complication of therapy, for an actuarial risk of 10% at 5 years. Only two patients required hospital admittance for treatment-related morbidity. CONCLUSIONS: These findings support the continued use of limb-preserving management for extremity sarcomas and emphasize the importance of the status of the surgical margins.

Adolescent↗
PubMed1993

Swallowing function in patients with esophageal cancer treated with concurrent radiation and chemotherapy.

BACKGROUND: Major goals of concurrent radiation and chemotherapy in the treatment of esophageal cancer are the early restoration and long-term maintenance of swallowing function. The purpose of this study was to determine the impact of concurrent radiation and chemotherapy on swallowing function. METHODS: Between September 1980 and September 1990, 120 patients with esophageal cancer were treated at the Fox Chase Cancer Center on the basis of one of three prospective nonrandomized protocols using concurrent chemotherapy and radiation. Swallowing function was retrospectively assessed in these patients by use of a swallowing-function scoring system. In addition, patients who had long-term control of their esophageal cancer underwent a more detailed analysis of swallowing function. RESULTS: Initial improvement in dysphagia occurred in 88% of the 102 assessable patients, with a median time to improvement of 2 weeks. There was no difference in overall percentage of initial improvement for patients with adenocarcinoma versus squamous cell carcinoma. Patients with distal tumors, however, showed both earlier and higher frequency of initial improvement than did patients with tumors in the upper two-thirds of the thoracic esophagus (95% versus 79%). Local relapse-free survival of definitively treated patients at 3 years was 60% and was significantly better for patients with Stage I (76%) versus Stage II cancers (55%) (P < 0.05). All 25 patients treated with curative intent who survived for more than 1 year without evidence of disease were able to eat soft or solid foods and had a benign stricture rate of only 12%. Even in patients with advanced disease who were treated with palliative intent, 91% had an initial improvement in swallowing function and 67% had improvement in swallowing function that lasted until death. CONCLUSIONS: High-dose concurrent radiation and chemotherapy provides rapid improvement in dysphagia, and this improvement results in normal or near-normal swallowing function of long duration.

Combined Modality Therapy↗
PubMed1993

The use of mitomycin in esophageal cancer.

Concurrent administration of chemotherapeutic agents and radiation with or without surgery has yielded better local disease control and more prolonged survival than has standard radiation therapy or surgery alone in patients with esophageal cancer. Combinations of 5-fluorouracil (5-FU) and either cisplatin or mitomycin have proven most effective in this setting. As a single agent, mitomycin has generated response rates of 14-42% in patients with squamous cell carcinoma of the esophagus. The response of patients with esophageal adenocarcinoma to single-agent mitomycin is unknown. The clinical use of mitomycin concurrent with 5-FU and radiation is well established in esophageal cancer. There is some experimental evidence to suggest that synergy may occur between 5-FU and mitomycin. Mitomycin is preferentially cytotoxic to hypoxic cells, which are relatively radioresistant. It is not clear whether use of mitomycin with radiation is additive or supra-additive as experimental evidence exists to support both types of interaction. Nonrandomized clinical trials suggest that using either cisplatin or mitomycin concurrently with 5-FU and relatively low-dose radiation (30 Gy) prior to esophagectomy can result in comparable rates of pathologic complete response (20-30%) and median survival (12-19 months). Hematologic toxicity is frequently severe if all 3 drugs are used concurrently in combination with radiation. In patients with advanced disease (stage III or IV), combination chemotherapy/radiation therapy can result in significant palliation with tolerable morbidity. The use of concurrent chemotherapy and radiation has changed the pattern of failure in esophageal cancer from one dominated by inability to control local disease to one where systemic failure predominates. Current and proposed trials in esophageal cancer have changed their focus accordingly to meet this new treatment challenge.

Adenocarcinoma↗
PubMed1992

Conservative management of extensive low-lying rectal carcinomas with transanal local excision and combined preoperative and postoperative radiation therapy. A report of a phase I-II trial.

Between 1986 and 1990, 16 patients were enrolled in a prospective Phase I/II study of transanal local excision and combined preoperative and postoperative radiation therapy (RT). All patients had biopsy-proven adenocarcinoma extending to within 6 cm of the anal verge and involvement of at least one third of the rectal circumference with tumor. Five of 16 patients (32%) had T3 tumors, and only two patients had T1 tumors. Patients received a single 500 cGy fraction of RT to the pelvis within 24 hours before surgery and underwent transanal excision followed by postoperative RT (median dose, 5040 cGy). With a median follow-up of 33 months, overall 3-year actuarial survival was 94%. Two patients had isolated local recurrences (both successfully salvaged), and four had distant metastases but maintained local control. The 3-year actuarial rates of continuous freedom from any relapse, continuous local control, and no evidence of disease at last follow-up were 53%, 80%, and 71%, respectively. Only three of 16 patients required colostomy, resulting in a 3-year actuarial colostomy-free rate of 77%. There was a trend toward a higher rate of relapse (P = 0.066) in patients with T3 tumors than those with T1 and T2 tumors. Sphincter-preserving therapy for low-lying rectal carcinomas using local excision and combined preoperative and postoperative RT is feasible, although improved local and adjuvant therapy is needed for patients with T3 lesions.

Adenocarcinoma↗
PubMed1992

The need for subspecialization: intraoperative radiation therapy.

Intraoperative radiation therapy represents a technically complex branch of radiation oncology which is undergoing intensive study. Further results of randomized Phase III trials must be available before IORT is established as an effective modality. The majority of residency training programs do not have IORT available and the use of IORT is not required for initial certification in radiation oncology. Residents could be educated in the principal concepts and the technical details of IORT and should be knowledgeable in the results of clinical trials in IORT. At the present time the leading investigators in IORT should consider offering a special research year or fellowship training in an appropriate residency training facility. If Phase III trials of IORT prove positive in a number of sites it is likely that this modality will become mainstream and then training in IORT should be required of all radiation oncology residents. Certainly there is insufficient evidence for subspecialty certification in IORT at the present time. However, one should not construe from this statement that special training in IORT is not required for its appropriate use. On the contrary, given the potential for morbidity and yet to be proven efficacy, special training in IORT should be undertaken in centers of excellence in IORT and patients treated with IORT should be entered in clinical trials whenever possible.

Humans↗