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1.
Clin Oncol (R Coll Radiol) ; 33(10): 627-637, 2021 10.
Article in English | MEDLINE | ID: mdl-34092462

ABSTRACT

AIMS: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes. RESULTS: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm3 and 57.4 (range 7.7-426.6) cm3, respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED3 for 4 cm3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively. CONCLUSION: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Radiotherapy, Intensity-Modulated , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/radiotherapy , Humans , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Middle Aged , Prescriptions , Radiosurgery/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies
2.
AJNR Am J Neuroradiol ; 41(6): 1070-1075, 2020 06.
Article in English | MEDLINE | ID: mdl-32467187

ABSTRACT

BACKGROUND AND PURPOSE: The Neck Imaging Reporting and Data System is a standardized reporting system intended to risk stratify patients treated for head and neck squamous cell carcinoma. The purpose of this study is to investigate the positive predictive value of the Neck Imaging Reporting and Data System categories 3 and 4 on posttreatment PET/CT in patients treated definitively for head and neck squamous cell carcinoma. MATERIALS AND METHODS: We retrospectively identified patients treated definitively for head and neck squamous cell carcinoma between 2006 and 2018. Patients whose posttreatment PET/CT scans were interpreted as Neck Imaging Reporting and Data System 3 (suspicious) or 4 (definitive recurrence) at the primary site, regional nodes, or at distant sites were included. The reference standard was histopathology or unequivocal imaging or clinical evidence of treatment failure. The positive predictive values of Neck Imaging Reporting and Data System 3 and 4 posttreatment PET/CT were calculated. RESULTS: Seventy-two of 128 patients with posttreatment PET/CT interpreted as Neck Imaging Reporting and Data System 3 at the primary site, regional nodes, or distant sites were proved to have treatment failure at the suspicious sites, yielding an overall positive predictive value of 56% (95% CI, 48%-65%). The positive predictive values of Neck Imaging Reporting and Data System 3 by subsite were as follows: primary site, 56% (44/79); regional nodes, 65% (34/52); and distant sites, 79% (42/53). All 69 patients with posttreatment PET/CT interpreted as Neck Imaging Reporting and Data System 4 had true treatment failure, yielding a positive predictive value of 100% (95% CI, 96%-100%): primary site, 100% (28/28); regional nodes, 100% (32/32); and distant sites, 100% (29/29). CONCLUSIONS: The positive predictive value of Neck Imaging Reporting and Data System 3 on posttreatment PET/CT is relatively low. Thus, Neck Imaging Reporting and Data System 3 findings should be confirmed with tissue sampling before instituting new salvage treatment regimens to avoid unnecessary overtreatment and its associated toxicities. Neck Imaging Reporting and Data System 4 reliably indicates recurrent disease.


Subject(s)
Neoplasm Recurrence, Local/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Treatment Failure
3.
AJNR Am J Neuroradiol ; 39(10): 1884-1888, 2018 10.
Article in English | MEDLINE | ID: mdl-30166429

ABSTRACT

BACKGROUND AND PURPOSE: FDG PET/CT has a high negative predictive value in patients with head and neck squamous cell carcinoma who responds completely to non-operative therapy. However, the treatment failure rate in patients with a partial but incomplete response is unclear. Our aim was to investigate the negative predictive value of the first posttreatment FDG-PET/CT in patients with head and neck squamous cell carcinoma with incomplete response interpreted as Neck Imaging Reporting and Data System (NI-RADS) category 2. MATERIALS AND METHODS: We retrospectively identified patients with head and neck squamous cell carcinoma treated with chemoradiation or radiation therapy with curative intent in our institution between 2008 and 2016. We included patients whose first posttreatment FDG-PET/CT was interpreted as showing marked improvement of disease but who had a mild residual mass or FDG avidity in either the primary tumor bed or lymph nodes (NI-RADS 2). The negative predictive value of FDG-PET/CT was calculated, including the 95% CI, using the Newcombe method. Two-year disease-free survival was the reference standard. RESULTS: Seventeen of 110 patients (15%) experienced locoregional treatment failure within 2 years of completing treatment, yielding a negative predictive value of 85% (95% Cl, 77%-90%). The most common location of tumor recurrence was the cervical lymph nodes (59%). The median time interval between completion of therapy and treatment failure was 10 months (range, 5-24 months). CONCLUSIONS: In patients with an incomplete response after treatment of head and neck squamous cell carcinoma, the negative predictive value of the first posttreatment FDG-PET/CT was 85%, which is lower than the 91% negative predictive value of FDG-PET/CT in patients with an initial complete response. Patients with an incomplete response (NI-RADS 2) should undergo more frequent clinical and imaging surveillance than patients with an initial complete response (NI-RADS 1).


Subject(s)
Neoplasm Recurrence, Local/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/pathology , Adult , Aged , Chemoradiotherapy , Disease-Free Survival , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/therapy , Treatment Failure
4.
Oral Oncol ; 61: 41-6, 2016 10.
Article in English | MEDLINE | ID: mdl-27688103

ABSTRACT

OBJECTIVE: It has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality of life (QOL) outcomes between definitive CRT and definitive TORS. MATERIALS AND METHODS: An observational comparison study was performed on 92 patients treated with TORS±adjuvant therapy and 46 patients treated with definitive CRT between July 2005 and January 2016. The Kaplan Meier method was used for survival analyses, and the Mann-Whitney test was used to compare QOL scores between groups. RESULTS: All patients had T0-T2 and N0-N2 disease, although CRT patients had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was 22.1months (range: 0.33-83.4). There were no significant differences in locoregional control or overall survival between CRT and TORS groups. Definitive TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and 24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067, p=0.008). CONCLUSION: Definitive CRT and definitive TORS offer similar rates of locoregional control, overall survival, and disease-free survival in patients with early stage OPSCC. TORS resulted in significantly better short and long-term saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and taste-related QOL compared to TORS alone.


Subject(s)
Carcinoma, Squamous Cell/therapy , Oropharyngeal Neoplasms/therapy , Quality of Life , Robotic Surgical Procedures , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/surgery , Treatment Outcome
5.
Ann Oncol ; 27(12): 2257-2262, 2016 12.
Article in English | MEDLINE | ID: mdl-27733374

ABSTRACT

BACKGROUND: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. PATIENTS AND METHODS: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m2 and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%). CONCLUSIONS: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted. REGISTERED CLINICAL TRIAL NUMBER: NCT00798655.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/administration & dosage , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/pathology , Cisplatin/adverse effects , Combined Modality Therapy , Disease-Free Survival , ErbB Receptors/antagonists & inhibitors , Female , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Staging , Panitumumab , Squamous Cell Carcinoma of Head and Neck
6.
Ann Oncol ; 27(8): 1594-600, 2016 08.
Article in English | MEDLINE | ID: mdl-27177865

ABSTRACT

BACKGROUND: We previously reported the safety of concurrent cetuximab, an antibody against epidermal growth factor receptor (EGFR), pemetrexed, and radiation therapy (RT) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In this non-comparative phase II randomized trial, we evaluated this non-platinum combination with or without bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Patients with previously untreated stage III-IVB SCCHN were randomized to receive: conventionally fractionated radiation (70 Gy), concurrent cetuximab, and concurrent pemetrexed (arm A); or the identical regimen plus concurrent bevacizumab followed by bevacizumab maintenance for 24 weeks (arm B). The primary end point was 2-year progression-free survival (PFS), with each arm compared with historical control. Exploratory analyses included the relationship of established prognostic factors to PFS and quality of life (QoL). RESULTS: Seventy-eight patients were randomized: 66 oropharynx (42 HPV-positive, 15 HPV-negative, 9 unknown) and 12 larynx; 38 (49%) had heavy tobacco exposure. Two-year PFS was 79% [90% confidence interval (CI) 0.69-0.92; P < 0.0001] for arm A and 75% (90% CI 0.64-0.88; P < 0.0001) for arm B, both higher than historical control. No differences in PFS were observed for stage, tobacco history, HPV status, or type of center (community versus academic). A significantly increased rate of hemorrhage occurred in arm B. SCCHN-specific QoL declined acutely, with marked improvement but residual symptom burden 1 year post-treatment. CONCLUSIONS: RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance, and enhance clinical benefit. Further development of cetuximab, pemetrexed, and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Cetuximab/administration & dosage , ErbB Receptors/genetics , Head and Neck Neoplasms/drug therapy , Pemetrexed/administration & dosage , Vascular Endothelial Growth Factor A/genetics , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cetuximab/adverse effects , Disease-Free Survival , ErbB Receptors/antagonists & inhibitors , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Male , Molecular Targeted Therapy , Neoplasm Staging , Pemetrexed/adverse effects , Quality of Life , Squamous Cell Carcinoma of Head and Neck , Vascular Endothelial Growth Factor A/antagonists & inhibitors
7.
Lung Cancer ; 81(3): 416-421, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23849982

ABSTRACT

BACKGROUND: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). METHODS: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). RESULTS: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. CONCLUSIONS: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Radiotherapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/mortality , Cetuximab , Combined Modality Therapy , Consolidation Chemotherapy , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Radiotherapy/adverse effects , Treatment Outcome
8.
AJNR Am J Neuroradiol ; 34(8): 1632-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23639557

ABSTRACT

BACKGROUND AND PURPOSE: Optimizing the utilization of surveillance PET/CT in treated HNSCC is an area of ongoing research. Our aim was to determine the negative predictive value of PET/CT in patients with treated head and neck squamous cell cancer and to determine whether negative PET/CT reduces the need for further imaging surveillance. MATERIALS AND METHODS: We evaluated patients with treated HNSCC who underwent posttreatment surveillance PET/CT. During routine clinical readouts, scans were categorized as having negative, probably negative, probably malignant, or malignant findings. We followed patients clinically and radiographically for at least 12 months from their last PET/CT (mean, 26 months; median, 28 months; range, 12-89 months) to determine recurrence rates. All suspected recurrences underwent biopsy for confirmation. RESULTS: Five hundred twelve patients (1553 scans) were included in the study. Two hundred fourteen patients had at least 1 PET/CT with negative findings. Of the 214 patients with a scan with negative findings, 19 (9%) eventually experienced recurrence, resulting in a NPV of 91%. In addition, a subgroup of 114 patients with 2 consecutive PET/CT examinations with negative findings within a 6-month period was identified. Only 2 recurrences were found in this group, giving a NPV of 98%. CONCLUSIONS: In patients treated for HNSCC, a single PET/CT with negative findings carries a NPV of 91%, which is not adequate to defer further radiologic surveillance. Two consecutive PET/CT examinations with negative findings within a 6-month period, however, resulted in a NPV of 98%, which could obviate further radiologic imaging in the absence of clinical signs of recurrence.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/prevention & control , Positron-Emission Tomography/statistics & numerical data , Sentinel Surveillance , Tomography, X-Ray Computed/statistics & numerical data , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/epidemiology , Female , Head and Neck Neoplasms/epidemiology , Humans , Male , Middle Aged , Multimodal Imaging , Neoplasm Recurrence, Local/epidemiology , Pennsylvania/epidemiology , Prevalence , Prognosis , Reproducibility of Results , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Squamous Cell Carcinoma of Head and Neck , Treatment Outcome
10.
Clin Oncol (R Coll Radiol) ; 24(6): 424-31, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22075444

ABSTRACT

AIMS: To report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network. MATERIALS AND METHODS: Seventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1-T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to a median dose of 55.8 Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: The median follow-up for the entire cohort was 16 months (range 0-72 months). Acute grade ≥3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively. CONCLUSIONS: Early results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/drug therapy , Anus Neoplasms/radiotherapy , Academic Medical Centers , Adult , Aged , Aged, 80 and over , Anus Neoplasms/pathology , Chemoradiotherapy , Cisplatin/administration & dosage , Community Health Centers , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Mitomycin/administration & dosage , National Cancer Institute (U.S.) , Radiotherapy, Intensity-Modulated/methods , Survival Analysis , Treatment Outcome , United States
11.
Technol Cancer Res Treat ; 10(3): 253-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21517131

ABSTRACT

Local tumor control remains a significant challenge in patients with glioblastoma multiforme (GBM). Despite aggressive radiation therapy approaches, most recurrences are within the high-dose field, limiting the ability to safely re-irradiate recurrence using conventional techniques. Fractionated stereotactic radiosurgery (fSRS) is a technique whose properties make it useful for re-irradiation. We retrospectively reviewed the charts of 14 patients with recurrent GBM treated with salvage radiosurgery. Seven patients were male and seven were female with a median age of 58 (range: 39-76). All patients had prior cranial radiation therapy to a median dose of 60 Gy (58-69). There were 18 lesions treated with a median tumor volume of 6.97 cm3 (0.54-50.0 cm3). fSRS was delivered in 1-3 fractions to a median dose of 24 Gy (18-30 Gy). Median follow-up for the cohort was 8 months (3-22 months). On follow-up MRI, 8 of 18 lesions had a radiographic response. The median time-to-progression following primary irradiation was 8 months (1-28 months) while the median time-to-progression (TTP) following fSRS was 5 months (1-16 months). Median local control following re-irradiation was 5 months and actuarial local control was 21% at 1-year. Overall survival following primary irradiation was 79% at 12 months and 46% at 2 years. Overall survival following re-irradiation was 79% at 6 months and 30% at 1 year. No significant treatment-related toxicity was seen in follow-up. These results indicate that re-irradiation for recurrent GBM using fSRS is well-tolerated and can offer a benefit in terms of progression-free survival (PFS).


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Glioblastoma/radiotherapy , Glioblastoma/surgery , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Radiosurgery , Adult , Aged , Brain Neoplasms/mortality , Female , Glioblastoma/mortality , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Survival Analysis , Treatment Outcome
12.
Ann Oncol ; 22(11): 2482-2488, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21363880

ABSTRACT

BACKGROUND: We studied the combination of pemetrexed, a multi-targeted antifolate, and cetuximab, an mAb against the epidermal growth factor receptor, with radiotherapy in poor prognosis head and neck cancer. PATIENTS AND METHODS: Patients received pemetrexed on days 1, 22, and 43 on a dose-escalation scheme with starting level (0) 350 mg/m(2) (level -1, 200 mg/m(2); level +1, 500 mg/m(2)) with concurrent radiotherapy (2 Gy/day) and cetuximab in two separate cohorts, not previously irradiated (A) and previously irradiated (B), who received 70 and 60-66 Gy, respectively. Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated. RESULTS: Thirty-two patients were enrolled. The maximum tolerated dose of pemetrexed was 500 mg/m(2) in cohort A and 350 mg/m(2) in cohort B. Prophylactic antibiotics were required. In cohort A, two dose-limiting toxicities (DLTs) occurred (febrile neutropenia), one each at levels 0 and +1. In cohort B, two DLTs occurred at level +1 (febrile neutropenia; death from perforated duodenal ulcer and sepsis). Grade 3 mucositis was common. No association of gene polymorphisms with toxicity or efficacy was evident. CONCLUSION: The addition of pemetrexed 500 mg/m(2) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/radiotherapy , Cetuximab , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Glutamates/administration & dosage , Glutamates/adverse effects , Guanine/administration & dosage , Guanine/adverse effects , Guanine/analogs & derivatives , Head and Neck Neoplasms/genetics , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Pemetrexed , Polymorphism, Genetic , Squamous Cell Carcinoma of Head and Neck , Thymidylate Synthase/genetics
14.
Technol Cancer Res Treat ; 9(5): 431-2, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20815414

Subject(s)
Radiosurgery , Robotics , Humans
15.
Ann Oncol ; 21(11): 2278-2283, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20430907

ABSTRACT

PURPOSE: RECIST have limitations when applied to potentially curable locally advanced squamous cell carcinoma of the head and neck (SCCHN). [¹8F]fluorodeoxyglucose-positron emission tomography (PET) scan may be useful in assessing treatment response and predicting patient outcome. PATIENTS AND METHODS: We studied patients with previously untreated stages III-IVb SCCHN treated with primary concurrent chemoradiotherapy on five prospective clinical trials. Response was assessed by clinical exam, computed tomography (CT), and PET portions of combined PET-CT scan ∼8 weeks after completion of chemoradiotherapy. RESULTS: Fifty-three patients were analyzed. Complete response (CR) was demonstrated in 42 patients (79%) by clinical exam, 15 (28%) by CT, and 27 (51%) by PET. CR as assessed by PET, but not as assessed by clinical exam or CT using RECIST, correlated significantly with progression-free status (PFS) (P < 0.0001). The 2-year PFS for patients with CR and without CR by PET was 93% and 48%, respectively (P = 0.0002). CONCLUSIONS: A negative PET scan on combined PET-CT after chemoradiotherapy is a powerful predictor of outcome in patients receiving curative chemoradiotherapy for SCCHN. PET-CT is indicated for response evaluation in this setting to improve the accuracy of post-treatment assessment by CT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Female , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/pathology , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Radiopharmaceuticals , Radiotherapy Dosage , Survival Rate , Treatment Outcome , Young Adult
16.
Ann Oncol ; 21(1): 145-51, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19602566

ABSTRACT

BACKGROUND: Patients treated with chemoradiotherapy (CRT) for head and neck cancers often require feeding tubes (FTs) due to toxicity. We sought to identify factors associated with a prolonged FT requirement. PATIENTS AND METHODS: We retrospectively reviewed 80 patients treated with CRT for head and neck cancers. The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx (GL) were contoured and the mean radiation doses and the volumes of each receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined. RESULTS: A total of 33 of 80 patients required a FT either before or during the course of CRT. Fifteen patients required the FT for > or = 6 months. On univariate analysis, significant factors associated with a prolonged FT requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3-T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as significant factors .The proportions of patients requiring a FT > or = 6 months were 8% and 28% for treatment plans with PC-V70 <30% and > or = 30%, respectively. CONCLUSIONS: Increased radiation dose to the PCs is associated with a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce this risk.


Subject(s)
Enteral Nutrition , Head and Neck Neoplasms/radiotherapy , Pharynx/radiation effects , Radiation Injuries/complications , Radiotherapy/adverse effects , Adult , Aged , Antineoplastic Agents/adverse effects , Combined Modality Therapy , Female , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Muscle, Smooth/radiation effects , Neoplasm Staging , Radiotherapy Dosage , Retrospective Studies , Time
17.
Clin Oncol (R Coll Radiol) ; 21(6): 483-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19423307

ABSTRACT

AIMS: To compare differences in dose to the target volume and organs at risk (OARs) for ring and tandem brachytherapy using individualised magnetic resonance imaging (MRI)/computed tomography-based three-dimensional treatment plans for each application vs plans based on a single scan for all fractions. MATERIALS AND METHODS: The study was carried out in 10 patients with carcinoma of the uterine cervix, treated with external beam radiotherapy and five fractions of high dose rate brachytherapy. Planning was carried out using MRI for the first fraction and computed tomography for each of the four subsequent fractions. The MRI-based plan was taken as the reference and the single-plan procedure was calculated by using the weights from the reference plan to calculate the dose distribution for each subsequent computed tomography-based plan. The high-risk clinical target volume (HRCTV) and OARs were delineated as per GEC-ESTRO guidelines. Total doses from external beam radiotherapy and brachytherapy were summated and normalised to a 2 Gy fraction size. RESULTS: The mean D(90) for the HRCTV was 81.9 Gy when using one plan and 84 Gy when using individual treatment plans. Similarly, the mean D(2 cc) was 75.68 Gy vs 74.99 Gy for the bladder, 55.84 Gy vs 56.56 Gy for the rectum and 64.8 Gy vs 65.5 Gy for the sigmoid. Ring rotation was identified in three patients, resulting in a change in dwell positions, which otherwise could have led to either a high bladder dose or suboptimal coverage of the HRCTV. CONCLUSIONS: Our study has shown that a single-plan procedure achieved acceptable dosimetry in most patients. However, the individualised plan improved dosimetry by accounting for variations in applicator geometry and the position of critical organs.


Subject(s)
Brachytherapy/methods , Radiotherapy Planning, Computer-Assisted/methods , Uterine Cervical Neoplasms/radiotherapy , Dose-Response Relationship, Radiation , Female , Humans , Magnetic Resonance Imaging/methods , Radiotherapy Dosage , Tomography, X-Ray Computed/methods , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology
18.
Cancer Invest ; 26(9): 936-47, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19034776

ABSTRACT

Cancer is one of the five leading causes of death in the Caribbean. Viral infections have been associated with cancer development and propagation, but the prevalence of such infections in the Caribbean is unknown. This review of the published literature shows that in 161,196 subjects from 14 Caribbean Islands, the adjusted prevalence of HHV8 infection is 4.5%, HTLV-1: 1.0%, HPV: 57.5%, HCV: 0.4%, HBV: 9.4%, and EBV: 92.2%. With the exception of HCV, the prevalence was significantly higher in the Caribbean than in the United States. These findings may significantly contribute to the high incidence of cancer observed in the Caribbean.


Subject(s)
Black People , Neoplasms/epidemiology , Neoplasms/virology , Virus Diseases/complications , Caribbean Region/epidemiology , Female , Humans , Incidence , Male , Prevalence , Seroepidemiologic Studies
19.
Ann Oncol ; 19(9): 1639-43, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18467311

ABSTRACT

BACKGROUND: The effect of prior treatment with radiotherapy and/or chemotherapy on the myelotoxicity of samarium lexidronam (Sm 153) in patients with metastatic bone lesions and bone pain was described. METHODS: Single-institution retrospective chart review of patients receiving Sm 153. The effect of Sm 153 on peripheral white blood cell (WBC), platelet counts, and change from baseline was calculated. RESULTS: The available hematologic data from records of 58 patients receiving 100 treatments with Sm 153 were reviewed. Prior treatment with radiotherapy or chemotherapy had no effect on changes from baseline or median nadir counts for either WBC or platelets when compared with patients not having such prior treatments. Multiple treatments with Sm 153 had no effect on change from baseline in WBC or platelet counts as compared with the initial administration. Median survival following the first dose of Sm 153 was 15 months. CONCLUSIONS: Prior treatment with radiotherapy or chemotherapy did not affect the rates of myelotoxicity. Multiple treatments with samarium Sm 153 lexidronam also had no effect on severity of myelotoxicity with successive courses. Patients with bone predominant metastatic disease may survive for extended periods of time and may safely be treated with multiple modalities of therapy.


Subject(s)
Bone Marrow/pathology , Bone Neoplasms/radiotherapy , Organometallic Compounds/adverse effects , Organophosphorus Compounds/adverse effects , Palliative Care , Radioimmunotherapy/methods , Adult , Aged , Aged, 80 and over , Bone Marrow/drug effects , Bone Neoplasms/drug therapy , Bone Neoplasms/mortality , Bone Neoplasms/secondary , Cohort Studies , Confidence Intervals , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Kaplan-Meier Estimate , Leukocytes/drug effects , Male , Middle Aged , Neoadjuvant Therapy , Neoplasms/drug therapy , Neoplasms/mortality , Neoplasms/pathology , Neoplasms/radiotherapy , Organometallic Compounds/therapeutic use , Organophosphorus Compounds/therapeutic use , Pain/pathology , Pain/radiotherapy , Pain Measurement , Platelet Count , Probability , Prognosis , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome
20.
Biomed Imaging Interv J ; 4(3): e40, 2008 Jul.
Article in English | MEDLINE | ID: mdl-21611006

ABSTRACT

New cases of invasive cancer in the United States occur among nearly 1.5 million people annually. In 2007, more than 1,500 people died per day with this diagnosis. Cancer is responsible for nearly one in every four deaths reported in the country. Enormous amounts of money and research have been, and are being spent, in an attempt to improve these numbers. While prevention and early detection remain the key to long-term success, treatment in the neo-adjuvant, adjuvant and metastatic settings still centre around two main treatment modalities - radiation therapy and chemotherapy. This article will review the advances that have been made in both areas that are making these treatments more precise and convenient, as well as less toxic, for the patient. In the field of radiation therapy this involves the development of new therapy planning and delivery systems, such as intensity-modulated radiation therapy (IMRT), and positron emission and computed tomography, PET-CT. Chemotherapy has also evolved with the development of targeted chemotherapy for the treatment of specific malignancies as well as improved supportive care agents which allow for the administration of dose-dense chemotherapy when appropriate.

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