Biomedical subjects

Michael T Milano

Publications and source records attributed to Michael T Milano.

14 recordsLinked to original sources

PubMed2006

Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases.

PURPOSE: To evaluate the feasibility and efficacy of hypofractionated stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS AND MATERIALS: The records of 69 patients with 174 metastatic liver lesions treated with SBRT between April 2001 and October 2004 were reviewed. The most common primary tumors were colorectal (n = 20), breast (n = 16), pancreas (n = 9), and lung (n = 5). The mean number of lesions treated per patient was 2.5 (range, 1-6). The longest diameter of the lesions ranged in size from 0.6 to 12.2 cm (median, 2.7 cm). Dose per fraction ranged from 2 Gy to 6 Gy, with a median total dose of 48 Gy (range, 30-55 Gy). Dose was prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor volume with a minimum margin of 7 mm. RESULTS: The median follow up was 14.5 months. Sixty patients were evaluable for response based on an abdominal computed tomography scan obtained at a minimum of 3 months after completion of SBRT. The actuarial overall infield local control rate of the irradiated lesions was 76% and 57% at 10 and 20 months, respectively. The median overall survival time was 14.5 months. The progression-free survival rate was 46% and 24% at 6 and 12 months, respectively. None of the patients developed Grade 3 or higher toxicity. CONCLUSION: Hypofractionated SBRT provides excellent local control with minimal side effects in selected patients with limited hepatic metastases.

Adult↗

PubMed2006

Intensity-modulated versus conventional pelvic radiotherapy for prostate cancer: analysis of acute toxicity.

OBJECTIVES: To provide a single-institution analysis of the influence of pelvic intensity-modulated radiotherapy (RT) on acute genitourinary (GU) and gastrointestinal (GI) toxicity. METHODS: The records of 610 consecutive patients with prostate cancer receiving RT were reviewed. Of these 610 patients, 49 had received a prostate boost preceded by pelvic RT (PRT), 15 intensity-modulated PRT (IM-PRT), and 34 four-field PRT (4F-PRT). The dosimetric endpoints for the bladder, rectum, and target for the PRT plans were compared using the paired t test; similar dosimetric analyses were done for the composite plans. Acute GU and GI toxicity were compared using the chi-square test. Ordered logit regression analyses were performed using all major treatment factors as covariates. RESULTS: The bladder and rectum dosimetric endpoints were improved for IM-PRT compared with 4F-PRT for the PRT portion of the treatment plan (P = 0.06 and P = 0.03, respectively) and for the composite treatment plan (P = 0.04 and P = 0.01, respectively), at the expense of greater target inhomogeneity in the PRT portion of the treatment plan (P < 0.01). GU toxicity was significantly lower in the IM-PRT group (P < 0.001), and GI toxicity was similar in both groups (P = 0.637). The regression analyses showed that intensity-modulated RT for the pelvic portion of treatment was the only factor significantly predicting for GU toxicity (P = 0.05); no major treatment factor reached significance in predicting GI toxicity. CONCLUSIONS: Compared with 4F-PRT, the use of IM-PRT improved dosimetric outcomes, was not associated with a reduction in acute GI toxicity, and was associated with a reduction in acute GU toxicity in the treatment of prostate cancer.

Aged↗

PubMed2006

Stereotactic Body Radiation Therapy (SBRT) for lung metastases.

The curative treatment of oligometastases with radiotherapy remains an area of active investigation. We hypothesise that treating oligometastases with SBRT can prolong life and potentially cure patients, while in patients with multiple lung metastases SBRT can improve quality of life. Fifty patients with lung metastases were treated on this study. Individuals with five or fewer total lesions were treated with curative intent. Individuals with > five metastases were treated palliatively. Most patients (62%) received 5 Gy/fraction for a total of 50 Gy. The number of targets treated per patient ranged from one to five (mean 2.6). Tumor sizes ranged from 0.3-7.7 cm in maximal diameter (median 2.1 cm). Mean follow-up was 18.7 months. Local control of treated lesions was obtained in 42 of 49 evaluable patients (83%). Of the 125 total lesions treated, eight progressed after treatment (94% crude local control). The median overall survival time from time of treatment completion of the curatively treated patients was 23.4 months. The progression-free survival of the same group of patients was 25% and 16% at 12 and 24 months, respectively. Grade 1 toxicity occurred in 35% of all the patients, 6.1% had grade 2 toxicity, and 2% had grade 3 toxicity. Excellent local tumor control rates with low toxicity are seen with SBRT. Median survival time and progression-free survival both appear better than that achieved with standard care alone. Long-term progression-free survival can be seen in a subset of patients when all tumors are targeted.

Adenocarcinoma↗

PubMed2006

Intensity-modulated radiation therapy in advanced head and neck patients treated with intensive chemoradiotherapy: preliminary experience and future directions.

We review our recent experience with intensity-modulated radiation therapy (IMRT) and conventional three-dimensional radiation therapy (C3DRT) in advanced head and neck cancer. Sixty-nine patients with Stage IV head and neck cancer (and stage III base of tongue and hypopharynx) enrolled in a Phase II study of definitive chemoradiation; 20 received all or part of their radiation with IMRT. Image-guided set-up, using video subtraction techniques, was used in all patients. Six weekly doses of induction carboplatin (AUC=2) and paclitaxel (135 mg/m2) were followed by alternating weekly chemoradiation to 75 Gy with 1.5 Gy BID fractions, concurrent with paclitaxel (100 mg/m2/week), 5-fluorouracil (600 mg/m2/d) and hydroxyurea (500 mg PO BID). Two consecutive cohorts enrolled, differing in radiation scheme: 75 Gy to gross disease in both, 60 or 54 Gy to first echelon lymphatics and 45 or 39 Gy to second echelon lymphatics. With a median follow-up of 47 months, 3-year overall survival is 68.5% and 3-year locoregional control is 94.0%, with no significant differences between those treated with C3DRT versus IMRT, nor between the two radiation dosing schemes. Actuarial overall survival without tracheostomy or laryngectomy, or without a gastrostomy tube was also similar. Acute mucositis, dermatitis and pain were similar with C3DRT and IMRT. Preliminary data suggests IMRT is well tolerated, and does not compromise locoregional control, indicating that IMRT adequately covers the clinical volume at risk. Building on the present clinical experience, future directions include more directed efforts at reducing toxicity, with better planning software and planning techniques.

Adult↗

PubMed2005

Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma.

PURPOSE: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. METHODS AND MATERIALS: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n=14), cisplatin plus FHX (n=23), paclitaxel plus FHX (n=42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n=26), and irinotecan plus FHX (n=10). RESULTS: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. CONCLUSION: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials.

Adult↗

PubMed2005

Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome.

PURPOSE: To assess survival, local control, and toxicity of intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the anal canal. METHODS AND MATERIALS: Seventeen patients were treated with nine-field IMRT plans. Thirteen received concurrent 5-fluorouracil and mitomycin C, whereas 1 patient received 5-fluorouracil alone. Seven patients were planned with three-dimensional anteroposterior/posterior-anterior (AP/PA) fields for dosimetric comparison to IMRT. RESULTS: Compared with AP/PA, IMRT reduced the mean and threshold doses to small bowel, bladder, and genitalia. Treatment was well tolerated, with no Grade > or =3 acute nonhematologic toxicity. There were no treatment breaks attributable to gastrointestinal or skin toxicity. Of patients who received mitomycin C, 38% experienced Grade 4 hematologic toxicity. IMRT did not afford bone marrow sparing, possibly resulting from the clinical decision to prescribe 45 Gy to the whole pelvis in most patients, vs. the Radiation Therapy Oncology Group-recommended 30.6 Gy whole pelvic dose. Three of 17 patients, who did not achieve a complete response, proceeded to an abdominoperineal resection and colostomy. At a median follow-up of 20.3 months, there were no other local failures. Two-year overall survival, disease-free survival, and colostomy-free survival are: 91%, 65%, and 82% respectively. CONCLUSIONS: In this hypothesis-generating analysis, the acute toxicity and clinical outcome with IMRT in the treatment of anal cancer is encouraging. Compared with historical controls, local control is not compromised despite efforts to increase conformality and reduce normal structure dose.

Adult↗

PubMed2005

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy.

PURPOSE: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. METHODS AND MATERIALS: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). RESULTS: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. CONCLUSION: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.

Adult↗

PubMed2005

Cellular response to DNA damage.

Eukaryotic cells, from yeast to man, possess evolutionarily conserved mechanisms to accurately and efficiently repair the overwhelming majority of DNA damage, thereby ensuring genomic integrity. Important repair pathways include base excision repair, nucleotide excision repair, mismatch repair, non-homologous end-joining, and homologous recombination. Defects in DNA repair processes generally result in susceptibility to cancer and, often, abnormalities in multiple organ systems. While signal transduction pathways have been intensely studied, epigenetic changes occurring in response to DNA damage are rapidly increasing in importance. Effective radiation and chemotherapy sensitization could result from selective inhibition of DNA repair in tumor cells. DNA damage repair is a dynamic field of research where the fruits of basic research often have important clinical implications.

DNA↗

PubMed2004

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, gemcitabine, and twice-daily radiation in patients with poor-prognosis cancer of the head and neck.

PURPOSE: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients. EXPERIMENTAL DESIGN: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m(2)/d, for 5 days; paclitaxel, 100 mg/m(2) on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50-300 mg/m(2) on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade > or =4 neutropenia or thrombocytopenia for >4 days; grade > or =4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed. RESULTS: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m(2) during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m(2) delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common. CONCLUSIONS: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

Adolescent↗

PubMed2004

Intensity-modulated radiotherapy and the Internet.

BACKGROUND: The objective of the current study was to evaluate the content and quality of patient-oriented information regarding intensity-modulated radiotherapy (IMRT) on the Internet. METHODS: IMRT websites were identified by reviewing the first 50 uniform resource locators on 5 search engines using the search terms IMRT and intensity modulated radiation therapy. Each site was evaluated by three observers for informational content, presentation, accuracy, and balance. A score of low, moderate, or high was assigned to each category based on a predefined scoring system. An overall score was assigned to each site, ranging from -35 to 100 points. RESULTS: Seventy-seven patient-oriented IMRT websites were identified (45% private, 21% academic, and 18% commercial). Most sites (58%) had a low level of informational content, with information on fundamental aspects of IMRT planning (target delineation and inverse planning) appearing on < 50% of sites. The most commonly discussed tumors were genitourinary (65%) and head and neck (53%) lesions. Few sites, however, described the potential benefits of IMRT (toxicity and tumor control). Most sites (82%) used patient-appropriate language. False and/or misleading information was seen on 42% of sites and was equally common on academic, private, and commercial sites. Balance statements were present on 24% of sites (most of which were commercial). The median overall score was 20 points (range, -25 to 70 points). The median overall scores for academic, private, commercial, and other sites were 10, 20, 25, and 20 points, respectively (P = 0.26). CONCLUSIONS: In general, the content and quality of patient-oriented information regarding IMRT on the Internet were poor. Patients and their physicians need to be aware of these problems when selecting treatment courses.

Humans↗

PubMed2004

Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome.

PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a pancreatic primitive neuroectodermal tumor received concurrent etoposide and ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning with conventional three-dimensional four-field techniques for dosimetric comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a median follow-up of 10.2 months, no resected patients had local failure, and only 1 of 10 assessable patients with unresectable cancer had local progression. The median survival and distant metastasis-free survival of the 24 patients with adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity occurred in 1 patient surviving >5 years. The remainder of the assessable patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In this hypothesis-generating analysis, the acute and chronic toxicity profile with IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local control was not compromised, despite efforts to increase conformality and avoid doses to normal structures. Distant failure remains a major obstacle in pancreatic cancer.

Adenocarcinoma↗

PubMed2004

Reirradiation of recurrent head and neck cancers with curative intent.

In patients with recurrent, previously irradiated head and neck cancer, the traditional therapy of palliative single- or multi-agent chemotherapy yields a 30% to 40% response rate with median survival durations of 8 to 10 months. However, long-term survival is rarely observed. Reirradiation with or without concurrent chemotherapy is currently under investigation as a treatment option in these patients. While reirradiation without chemotherapy appears to be effective in recurrent nasopharynx cancer cases, the use of concomitant chemotherapy with reirradiation appears to offer improved outcomes based on phase I/II data in other head and neck sites. Recent studies indicate that long-term survival of patients is possible following reirradiation in a minority of cases despite severe acute and chronic toxicities. Reirradiation with chemotherapy is appropriate for patients with a goal of long-term local control of disease and curative intent, despite the risk of significant acute and late toxicities.

Combined Modality Therapy↗

PubMed2003

Reirradiation of recurrent and second primary head and neck malignancies: a comprehensive review.

The management of locoregionally recurrent or second primary tumors in a previously irradiated head and neck volume presents a challenging clinical problem. Only a small subset of patients are candidates for potentially curative surgery. Chemotherapy alone provides only limited palliation with no long term survivors. Reirradiation, particularly with aggressive concomitant chemotherapy, results in prolonged median survival and long term survival for some patients. The toxicity of reirradiation, while greater than chemotherapy alone or primary irradiation, is lower than expected for the high cumulative radiation doses. The results of reirradiation in recurrent head and neck cancer and the prognostic factors predicting outcome in this patient population are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer.

PURPOSE: We sought to investigate CPT-11 as a promising agent to our established regimen of 5-fluorouracil (5-FU), hydroxyurea, and hyperfractionated radiation therapy. A phase I study was conducted to determine the maximum tolerated dose and dose-limiting toxicities of this regimen. PATIENTS AND METHODS: Eligible patients included patients with poor prognosis advanced head and neck cancer who required radiation therapy. All patients were treated on a 14-day cycle. Each patient received 5-FU (600 mg/m(2)/d), hydroxyurea (500 mg orally every 12 hours), radiation therapy twice daily (150 cGy each fraction), and CPT-11 at a starting dose of 5 mg/m(2)/d for 5 consecutive days followed by a 9-day break. CPT-11 was escalated in five mg/m(2)/d increments. Dose-limiting toxicity was defined as grade 4 hematologic toxicity, persistent grade 4 dermatitis and mucositis, grade 4 diarrhea despite maximal pharmacologic intervention, and inability to receive full-dose chemotherapy with the next cycle of treatment. Fourteen patients were treated at maximum tolerated dose to verify the recommended phase II dose. RESULTS: Between August 1998 and August 2001, 31 patients with advanced and/or recurrent head and neck cancer were enrolled. Cohorts of nine, four, three, and 14 patients were treated at 5-, 10-, 15-, and 10-mg/m(2)/d dose levels of CPT-11. The 5- and 10-mg/m(2)/d dose levels were well tolerated All three patients treated at 15 mg/m(2)/d experienced neutropenic dose-limiting toxicity during cycles 1-2. DISCUSSION: The maximum tolerated dose and recommended phase II dose of CPT-11 with hyperfractionated radiation therapy is 10 mg/m(2)/d.

Adult↗