Biomedical subjects

Michael G Haddock

Publications and source records attributed to Michael G Haddock.

30 records · Page 2Linked to original sources

PubMed2003

A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer.

PURPOSE: In vitro studies suggest that low-dose gemcitabine sensitizes cells to radiation therapy and that this effect persists for 48 h after drug exposure. Cisplatin is a radiation sensitizer and is also synergistic with gemcitabine in some in vitro tumor systems. Gemcitabine's radiosensitizing properties can theoretically be exploited by twice-weekly administration. This study assessed toxicity in patients with pancreatic cancer treated with radiation therapy, gemcitabine, and cisplatin. METHODS AND MATERIALS: Patients with locally advanced pancreatic or gastric cancer were eligible. Gemcitabine and cisplatin were given twice weekly for 3 weeks during radiation therapy (50.4 Gy in 28 fractions). The starting dose of gemcitabine was 5 mg/m(2) i.v. The starting dose for cisplatin was 5 mg/m(2). Chemotherapy doses escalated every 3 to 6 patients according to a standard Phase I study design. RESULTS: Twenty-four evaluable patients, all with pancreatic cancer, were treated on this protocol. Grade 3 neutropenia occurred in 2 patients, Grade 3 thrombocytopenia occurred in 2, and Grade 4 lymphopenia occurred in 1. There was no clear relationship between chemotherapy dose and hematologic toxicity. The most common Grade 3-4 nonhematologic toxic responses were vomiting (7 patients) and nausea (7 patients). Dose-limiting toxicity consisting of Grade 4 nausea and vomiting occurred in 2 of 3 patients at dose Level 6 (gemcitabine 45 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.) without dose-limiting toxicity. CONCLUSION: Gemcitabine 30 mg/m(2) i.v. twice weekly and cisplatin 10 mg/m(2) i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity.

Adenocarcinoma↗

PubMed2003

Rectal cancer: Preoperative versus postoperative irradiation as a component of adjuvant treatment.

The search for improved disease control and survival for resectable but high-risk rectal cancers has led to studies that combine all 3 modalities. For surgically resected, high-risk rectal cancers, postoperative chemoradiation has been shown to improve both disease control (local and distant) and survival (disease free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health Colorectal Cancer Consensus Conference. Three randomized studies showed improved overall survival (OS) and local control for patients treated with postoperative irradiation and chemotherapy when compared with surgery alone or surgery plus irradiation control arms. These include 2 US trials, Gastrointestinal Tumor Study Group and Mayo/North Central Cancer Treatment Group (NCCTG) and a Norway trial. Although most preoperative external beam radiation trials show reductions in local relapse with the addition of preoperative EBRT to resection, only the large Swedish trial of approximately 1,100 patients showed a survival improvement when compared with a surgery alone control arm for resectable primary rectal cancers. In a recent pooled analysis of 3 postoperative adjuvant rectal cancer trials (NCCTG 794751, NCCTG 864751, and GI Intergroup 0114) survival and disease relapse were dependent on both TN and NT stage of disease (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more positive nodes), T substage influenced 5-year OS (T1-2, 69%; T3, 48%; and T4, 38%; P <.001). Ongoing randomized trials are being conducted for patients with high-risk, resectable primary rectal cancers. The intent is to help define optimal combinations of postoperative chemoradiation (US GI Intergroup), to test sequencing issues of preoperative versus postoperative chemoradiation (Germany trial), and to determine if concurrent and maintenance 5-FU and leucovorin add to the benefits found with preoperative irradiation (European Organization for Research and Treatment of Cancer). For subsequent trials, it may be preferable to perform separate studies, or a planned statistical analysis, for different risk groups of patients (low, intermediate, moderately high, and high), as defined in the rectal cancer pooled analysis.

Chemotherapy, Adjuvant↗

PubMed2003

Intraoperative radiotherapy in the multimodality approach to colorectal cancer.

The addition of intraoperative radiotherapy (IORT) to the multimodality approach for the treatment of locally advanced and locally recurrent colorectal cancer seems to result in improvements in local control and long-term survival. Local control and survival are most likely in patients in whom a gross total resection is accomplished. Peripheral nerve is the dose-limiting structure for patients treated with IORT. Further improvements in local control require the addition of dose modifiers during external beam radiotherapy or IORT. Distant relapse remains problematic, and effective systemic therapy is necessary to significantly improve long-term survival.

Colectomy↗

PubMed2003

Endocavitary radiation therapy for rectal adenocarcinoma: 10-year results.

Local control, survival, and toxicity in patients treated with endocavitary radiation therapy for rectal cancer were evaluated. Thirty-five patients received a total of 20 to 155 Gy in 1 to 5 fractions with 50 kV x-rays through a treatment proctoscope. Twenty-nine of the 35 patients were treated with curative intent. Median follow-up was 102 months. Local control was achieved in 23 of the 29 patients treated curatively and in 3 of the 6 treated palliatively. Local control for patients treated curatively was 76% at 10 years. No local failures occurred after 21 months. For patients treated curatively, survival was 65% at 5 years and 42% at 10 years. Toxicity within 90 days after treatment was observed in 77% of the patients. Toxicity occurring more than 90 days after treatment was observed in 80%, but only 1 patient needed a colostomy, which was for a perforation after the biopsy of a benign ulcer. In conclusion, radiation therapy resulted in a local control rate of 76% at 10 years in curatively treated patients. Although most patients experience toxicity from this treatment, loss of sphincter function is rare.

Adenocarcinoma↗

PubMed2003

Curative potential of multimodality therapy for locally recurrent rectal cancer.

OBJECTIVE: To assess the results of multimodality therapy for patients with recurrent rectal cancer and to analyze factors predictive of curative resection and prognostic for overall survival. SUMMARY BACKGROUND DATA: Locally recurrent rectal cancer is a difficult clinical problem, and radical treatment options with curative intent are not generally accepted. METHODS: A total of 394 patients underwent surgical exploration for recurrent rectal cancer. Ninety were found to have unresectable local or extrapelvic disease and 304 underwent resection of the recurrence. The latter patients were prospectively followed to determine long-term survival and factors influencing survival. RESULTS: Overall 5-year survival was 25%. Curative, negative resection margins were obtained in 45% of patients; in these patients a 5-year survival of 37% was achieved, compared to 16% (P <.001) in patients with either microscopic or gross residual disease. In a logistic regression analysis, initial surgery with end-colostomy and symptomatic pain (both univariate) and increasing number of sites of the recurrent tumor fixation in the pelvis (multivariate) were associated with palliative surgery. Overall survival was significantly decreased for symptomatic pain (P <.001) and more than one fixation (P =.029). Survival following extended resection of adjacent organs was not different from limited resection (28% vs. 21%, P =.11). Patient demographics and factors related to the initial rectal cancer did not affect outcome. Perioperative mortality was only 0.3%, but significant morbidity occurred in 26% of patients, with pelvic abscess being the most common complication. CONCLUSIONS: This study demonstrates that many patients with locally recurrent rectal cancer can be resected with negative margins. Long-term survival can be achieved, especially for patients with no symptoms and minimal fixation of the recurrence in the pelvis, provided no gross residual disease remains.

Adult↗

PubMed2002

Electronic and film portal images: a comparison of landmark visibility and review accuracy.

PURPOSE: To quantitatively compare a scanning liquid ion chamber electronic portal imaging device (SLIC-EPID) and an amorphous silicon flat panel (aSi) EPID with portal film in clinical applications using measures of landmark visibility and treatment review accuracy. METHODS AND MATERIALS: Six radiation oncologists viewed 39 electronic portal images (EPIs) from the SLIC-EPID, 36 EPIs from the aSi-EPID, and portal films of each of these treatment fields. The physicians rated the clarity of anatomic landmarks in the portal images, and the scores were compared between EPID and film. Nine hundred portal image reviews were performed. EPID and film portal images were acquired with known setup errors in either phantom or cadaver treatments. Physicians identified the errors visually in portal films and with computerized analysis for EPID. RESULTS: There were no statistically significant (p < 0.05) differences between film and SLIC-EPID in ratings of landmark clarity. Eleven of 12 landmarks were more visible in aSi-EPID than in film. Translational setup errors were identified with an average accuracy of 2.5 mm in film, compared to 1.5 mm with SLIC-EPID and 1.3 mm with aSi-EPID. CONCLUSIONS: Both EPIDs are clinically viable replacements for film, but aSi-EPID represents a significant advancement in image quality over film.

Movement↗

PubMed2002

The relevance of prostatectomy findings for brachytherapy selection in patients with localized prostate carcinoma.

BACKGROUND: The efficacy of brachytherapy for patients with localized prostate carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and its subclinical extraprostatic extensions. Predictive models based on pretherapy factors may be useful to estimate the likelihood for clinically relevant extraprostatic disease and may be incorporated into selection criteria for this procedure. METHODS: Multivariate logistic regression model building was performed using pretherapy factors in 2905 surgically staged patients with localized prostate carcinoma to estimate the probability of seminal vesicle and/or lymph node involvement. Bootstrap methods were employed to assess the stability of the final model parameters and to determine the sensitivity and specificity of the final model. RESULTS: Clinical tumor classification, biopsy Gleason score groupings, and serum prostate specific antigen (PSA) levels were associated with seminal vesicle and/or pelvic lymph node involvement. These factors were incorporated into a multivariate model that predicted for these adverse histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle and/or pelvic lymph node involvement, patients with tumors classified as T1c-T2a, Gleason scores of 2-6, and PSA < or = 16 ng/mL; or with tumors classified as T1c-T2a, Gleason scores of 7-10, and PSA < or = 4 ng/mL; or with tumors classified as T2b-T2c, Gleason scores of 2-6, and PSA < or = 6 ng/mL would be potential candidates for brachytherapy alone. CONCLUSIONS: The predictive model presented may provide criteria whereby an adequately performed prostate brachytherapy procedure is expected to encompass the intraprostatic and adjacent extraprostatic disease. Prostate brachytherapy alone may be considered in these circumstances, whereas the addition of external beam radiotherapy may be reserved for patients with disease that is apt to extend beyond the brachytherapy target volume.

Brachytherapy↗

PubMed2002

Chemotherapy, irradiation, and surgery for function-preserving therapy of primary extremity soft tissue sarcomas: initial treatment with ifosfamide, mitomycin, doxorubicin, and cisplatin plus granulocyte macrophage-colony-stimulating factor.

BACKGROUND: Most institutional teams utilize multimodality therapy in their efforts to cure patients with primary high-grade extremity soft tissue sarcomas, although the value of adjuvant systemic chemotherapy is still disputed by some oncologists. This single-institution Phase II study describes an effort to control metastasis by the use of two cycles of chemotherapy as the initial preoperative treatment. METHODS: Between March 1994 and October 1997, 20 women and 19 men with primary extremity or limb girdle high-grade soft tissue sarcomas were registered to a study of preoperative ifosfamide, mitomycin, doxorubicin, cisplatin (IMAP) plus granulocyte macrophage-colony-stimulating factor (GM-CSF) followed by preoperative irradiation and subsequent limb-sparing surgery. The two sequential monthly cycles of IMAP involved intravenous ifosfamide, 2500 mg/m(2), and mesna, 2500 mg/m(2), on Day 0, followed by identical doses of these agents plus intravenous mitomycin, 4 mg/m(2), doxorubicin, 40 mg/m(2), and cisplatin, 60 mg/m(2), on Day 1. Sargramostim (GM-CSF) 250 microg/m(2) was given subcutaneously every 12 hours for 4 days beginning 6 days before the chemotherapy, and then for 14 more days beginning the day after chemotherapy was completed. At the beginning of the third month, external beam irradiation was administered daily, 5 days each week for 5 consecutive weeks to total preoperative doses of 4500 centigrays (cGy). This was accompanied by reduced doses of MAP chemotherapy (mitomycin, 6 mg/m(2), doxorubicin, 30 mg/m(2), and cisplatin, 45 mg/m(2)) intravenously on Days 0, 21, and 42 of the radiation therapy segment. Approximately 1 month after preoperative irradiation ended, each patient had complete surgical excision with curative intent, using limb-sparing techniques when possible. Radiation to total doses of 5500-6500 cGy was accomplished by delivery of an additional 1000-2000 cGy to the tumor bed via intraoperative electron beam, brachytherapy, or external beam irradiation at the completion of surgery. RESULTS: All except 5 patients had tumors at least 5 cm in diameter. Chemotherapy toxicity grade three or higher consisted primarily of vomiting (23%), leukopenia (54%), and thrombocytopenia (77%). Six patients have died of metastatic sarcoma, and one other died in a motorcycle accident. Kaplan-Meier curves indicate estimated 5-year survival of approximately 80% and freedom from metastasis at 2 years of approximately 85%. CONCLUSIONS: IMAP plus GM-CSF is satisfactory as initial treatment for primary extremity soft tissue sarcomas in two monthly cycles preceding irradiation. The prescribed irradiation was generally tolerable and effective in permitting limb-sparing surgery. Although the outcome of patients treated on this regimen has been favorable, the metastasis problem has not been eliminated.

Adult↗

PubMed2002

Use of intraoperative electron beam radiotherapy in the management of retroperitoneal soft tissue sarcomas.

PURPOSE: To evaluate the disease control, survival results, and tolerance of intraoperative electron beam radiotherapy (IOERT) as a component of treatment for retroperitoneal soft tissue sarcomas. METHODS AND MATERIALS: Between March 1981 and September 1995, 87 patients with primary (n = 43) or recurrent (n = 44) retroperitoneal or intrapelvic sarcomas received IOERT as a component of treatment at the Mayo Clinic. The tumors were high grade in 54 patients (62%) and low grade in 33 (38%). The median tumor size was 10 cm (range 2-36). All patients underwent maximal surgical resection with IOERT; in 72 patients, only microscopic or no residual tumor remained. The IOERT doses ranged from 8.75 to 30 Gy (median 15). All primary tumors received external beam irradiation (EBRT) with a median dose of 48.6 Gy. Thirty-four of the 44 recurrent tumors received EBRT to a median dose of 45 Gy. All patients were followed prospectively for outcome and toxicity evaluation. RESULTS: The median follow-up, based on 46 patients (53%) currently alive, was 3.5 years. The overall estimated 5-year survival was 47%. For patients with tumors > or = 10 cm, the 5-year overall survival was significantly poorer (28%) than for those with smaller lesions (60%) (p = 0.01). Neither primary vs. recurrent status nor tumor grade had a significant impact on survival. Patients with gross residual tumor had a marginally significantly poorer survival compared with patients with microscopic or no residual tumor, with a 5-year survival rate of 37% and 52%, respectively (p = 0.08). A total of 49 patients (56%) experienced failure, including 20 local recurrences (23%). The median time to failure was 2.3 years. Four recurrences were within the IOERT field, 3 within the IOERT and EBRT field, and 13 within the EBRT field alone. The 3- and 5-year estimated local control rate was 77% and 59%, respectively. Local control was marginally significantly affected by the amount of residual tumor, with a 5-year local control rate of 41% for those with gross residual tumor, 60% for those with microscopic residual tumor, and 100% for those with no residual tumor (p = 0.09). Gastrointestinal complications were recorded in 12 incidences (Grade 3 or higher toxicity). These complications were believed to be secondary to surgery and/or EBRT in 10 of the 12 cases. Seven patients had fistula formation, and 3 experienced severe proctitis. Grade 3 peripheral neurologic toxicities occurred in 9 patients (10%), but none had pain as a component of their neuropathy. CONCLUSION: Retroperitoneal soft tissue sarcomas can be treated with an aggressive combined approach of EBRT, surgery, and IOERT, with acceptable toxicity. Local control in primary disease appears to be improved in this retrospective series with this approach. Distant disease control and options for recurrent disease needs further definition.

Adolescent↗

PubMed2002

Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma.

PURPOSE: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5-fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. RESULTS: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p < 0.02). For patients with no residual disease, 5-year survival was 64% vs. 0% for those with residual disease (p = 0.002). The median survival was 0.6, 1.4, and 5.1 years for patients with gross residual, microscopic residual, and no residual disease, respectively (p = 0.02). The 5-year local control rate for the entire cohort was 73%. Two-year local control rates were 0%, 80%, and 88% for patients with gross residual, microscopic residual, or no residual disease, respectively (p < 0.01). Five-year local control rates were 100% for the 6 patients who received total EBRT doses >54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). CONCLUSION: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5-fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration of new cancer treatment modalities will be required to favorably impact on the poor prognosis of patients with Stage IV or subtotally resected GBC. Additional investigation leading to earlier diagnosis is warranted, because most patients with GBC present with advanced disease.

Adenocarcinoma↗

PubMed2002

Stage IIIC endometrioid corpus cancer includes distinct subgroups.

OBJECTIVE: Because stage IIIC corpus cancer is a heterogeneous substage, the outcomes of patients with stage IIIC disease were assessed according to the extent of extrauterine disease. METHODS: From 1984 through 1993, 51 patients with surgical stage IIIC corpus cancer were treated at our institution; 5 patients had tumors with nonendometrioid histologic features and were excluded from the analyses. Of the 46 patients with endometrioid carcinoma, 22 had lymph nodes as the only site of extrauterine disease (stage IIIC(0)) and 24 also had peritoneal cytologic, uterine serosal, adnexal, or vaginal involvement or a combination of these (stage IIIC(ab)). The mean number of lymph nodes removed was 18 pelvic and 8 aortic nodes. Median follow-up for surviving patients was 84 months. RESULTS: Patients with stage IIIC(0) cancer had a 5-year cause-specific survival (CSS) of 72% and a 5-year recurrence-free survival (RFS) of 68%, and those with stage IIIC(ab) had a CSS of 33% and an RFS of 25% (P < 0.01). Of the 22 patients with stage IIIC(0) endometrioid cancer, 21 had adjuvant radiotherapy (1 also received chemotherapy) and 1 was not treated. Relapse occurred in 7 (32%) patients, with only 1 having an initial failure component outside the node-bearing areas (lung). Of the 24 patients with stage IIIC(ab) cancer, 16 received adjuvant radiotherapy (1 had concomitant chemotherapy), 2 had chemotherapy, 4 had hormonal therapy, and 2 were not treated. We observed 16 recurrences (67%). Of the 14 patients with known initial sites of failure, 9 had an extranodal failure component. CONCLUSION: Assessment of CSS, RFS, and sites of relapse suggests that FIGO surgical stage IIIC endometrioid corpus cancer includes two distinct and readily separable subgroups: (1) stage IIIC(0), nodal involvement only, and (2) stage IIIC(ab), nodal plus cytologic, uterine serosal, adnexal, or vaginal involvement, or a combination of these. Our results also suggest that different treatment strategies are needed for these subgroups.

Adult↗

PubMed2002

The Mayo Clinic experience with multimodality treatment of locally advanced or recurrent colon cancer.

BACKGROUND: Patients with incompletely resected locally advanced and recurrent colon cancers have a dismal prognosis. Since 1981, 100 colon cancer patients have been treated with combination therapy including surgical resection, chemotherapy, and external plus intraoperative radiotherapy. METHODS: A prospective computerized intraoperative radiation database identified patients for this retrospective review. Data collection included patient demographics, tumor and treatment variables, and morbidity, recurrence, and survival statistics. RESULTS: The mean age was 55.2 years. Follow-up was available for all patients. Fifty-nine patients have died. Median follow-up of survivors was 70.5 months. Twenty-five patients with locally advanced colon cancer had a median survival of 38.2 months and a 5-year survival of 49%. Eleven of these patients are still free of disease. Seventy-three patients treated for recurrent colon carcinoma had a median survival of 33.3 months from the time of recurrence, with a 5-year survival of 24.7%. Twenty-one are alive without evidence of recurrence. The 38 patients with recurrent disease whose disease was completely resected had a 37.4% 5-year survival. CONCLUSIONS: A multimodality approach using en-bloc surgical resection with radiotherapy and chemotherapy affords some patients with locally advanced and recurrent colon cancer a chance for long-term survival.

Adult↗