-
[show abstract]
[hide abstract]
ABSTRACT: Report of clinical cancer control outcomes on Radiation Therapy Oncology Group (RTOG) 9406, a three-dimensional conformal radiation therapy (3D-CRT) dose escalation trial for localized adenocarcinoma of the prostate.
RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer. Patients were registered on five sequential dose levels: 68.4 Gy, 73.8 Gy, 79.2 Gy, 74 Gy, and 78 Gy with 1.8 Gy/day (levels I-III) or 2.0 Gy/day (levels IV and V). Neoadjuvant hormone therapy (NHT) from 2 to 6 months was allowed. Protocol-specific, American Society for Therapeutic Radiation Oncology (ASTRO), and Phoenix biochemical failure definitions are reported.
Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable. Median follow-up for levels I, II, III, IV, and V was 11.7, 10.4, 11.8, 10.4, and 9.2 years, respectively. Thirty-six percent of patients received NHT. The 5-year overall survival was 90%, 87%, 88%, 89%, and 88% for dose levels I-V, respectively. The 5-year clinical disease-free survival (excluding protocol prostate-specific antigen definition) for levels I-V is 84%, 78%, 81%, 82%, and 82%, respectively. By ASTRO definition, the 5-year disease-free survivals were 57%, 59%, 52%, 64% and 75% (low risk); 46%, 52%, 54%, 56%, and 63% (intermediate risk); and 50%, 34%, 46%, 34%, and 61% (high risk) for levels I-V, respectively. By the Phoenix definition, the 5-year disease-free survivals were 68%, 73%, 67%, 84%, and 80% (low risk); 70%, 62%, 70%, 74%, and 69% (intermediate risk); and 42%, 62%, 68%, 54%, and 67% (high risk) for levels I-V, respectively.
Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer. This multi-institutional experience allows comparison to other experiences with modern radiation therapy.
International journal of radiation oncology, biology, physics 07/2012; 83(3):e363-70. · 4.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: We aimed to determine the effects of systemic inflammation and symptoms of head and neck cancer patients on dietary intake and weight in relation to mode of treatment. METHODS: In all, 38 orally fed patients had intake, weight, C-reactive protein (CRP), and symptoms prospectively assessed at baseline, post-treatment, and follow-up. RESULTS: Intake/weight declined and CRP increased substantially in chemoirradiation patients (-11.4 ± 5.2 kg, -1214 kcal/day, 23.4 ± 24.9 mg/L; p < .05) versus radiotherapy patients (-3.5 ± 4.8 kg, -483 kcal/day, 8.3 ± 13.9 mg/L) during posttreatment (repeated-measures ANOVA). Multivariate generalized estimating equations modeling identified reduced swallowing capacity was a key predictor of energy intake in both treatment groups (p < .001); multiple symptoms experienced by radiotherapy/chemoirradiation patients were significant predictors of weight loss; additionally, in chemoirradiation patients, CRP was an independent predictor of weight loss (p < .001). CONCLUSIONS: Treatment of symptoms and systemic inflammation are important clinical targets to manage weight loss in patients with head and neck cancer, especially those treated with chemoirradiation. Head Neck, 2012.
Head & Neck 06/2012; · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: The purpose of this study was to test the validity of the Head and Neck Patient Symptom Checklist (HNSC). METHODS: Three hundred and sixty-eight treatment-naive individuals with head and neck cancer prospectively completed the HNSC and the Patient-Generated Symptom Global Assessment (PG-SGA). The predictive validity was determined by comparing the HNSC symptoms interference scores to the PG-SGA scores. Multivariate logistic regression was used to determine the HNSC symptoms scores associated with reduced dietary intake, ≥5 % weight loss over 6 months, and reduced functional performance (FP). RESULTS: HNSC sensitivity (79-98 %), specificity (99-100 %), positive predictive value (92-100 %), and negative predictive value (94-100 %) were excellent, and the Cronbach's alpha coefficient was 0.92. The multivariate logistic regression showed that advanced tumor stage, pain, loss of appetite (LOA), and difficulty swallowing significantly predicted dietary intake. Advanced tumor stage, LOA, and difficulty swallowing were also significant predictors of ≥5 % weight loss over 6 months. LOA, difficulty swallowing, feeling full, and lack of energy were significant predictors of reduced FP. CONCLUSIONS: The HNSC appears to be a valid tool for determining symptoms interfering with dietary intake of head and neck cancer (HNC) patients. This instrument may aid in early identification of symptoms that place HNC patients at risk for reductions in dietary intake, weight, and functional performance.
Supportive Care in Cancer 05/2012; · 2.09 Impact Factor
-
Lisa Capelle,
Heather Warkentin,
Marc Mackenzie,
Kurian Joseph,
Zsolt Gabos,
Nadeem Pervez,
Keith Tankel,
Susan Chafe,
John Amanie,
Sunita Ghosh, Matthew Parliament,
Bassam Abdulkarim
[show abstract]
[hide abstract]
ABSTRACT: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT).
Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients.
With HT there was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin(V50) (1.4% vs 5.9%, respectively; P=.001) but higher skin(V40) and skin(V30) (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans.
The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients receiving adjuvant breast RT.
International journal of radiation oncology, biology, physics 05/2012; 83(5):e583-90. · 4.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to evaluate the accuracy and precision of the Clarity 3D ultrasound system to track prostate gland positional variations due to setup error and organ motion. Seventeen patients (n = 17) undergoing radical external beam radiation therapy for localized prostate cancer were studied. Subsequent to initial reference ultrasound and planning CT scans, each patient underwent seven repeat weekly tracking CT and ultrasound (US) scans during the course of treatment. Variations in the location of the prostate between reference and tracking scans were measured. Differences reported by CT and ultrasound scans are compared. Ultrasound tracking was initially performed clinically by a group of trained general users. Retrospective prostate localization was then performed by a trained dedicated user upon the original raw data set and also a reduced data set derived from the original by an expert user from Resonant Medical. Correlation accuracy between ultrasound and CT shifts acquired and delineated by a pool of trained general users was deemed unacceptable for radiotherapy purposes. A mean discrepancy between CT and US localizations of greater than 10 mm, with a 5 mm or greater discrepancy rate of nearly 90%, was observed. Retrospective analysis by a dedicated user of both the original and Resonant Medical reduced data sets yielded mean CT-Us discrepancies of 8.7 mm and 7.4 mm, respectively. Unfortunately, the 5 mm or greater CT-US discord rate for these retrospective analyses failed to drop below 80%. The greatest disparity between CT and ultrasound was consistently observed in the superior-inferior direction, while greatest agreement was achieved in the lateral dimension. Despite an expert reanalysis of the original data, the Clarity ultrasound system failed to deliver an acceptable level of geometric accuracy required for modern radiotherapy purposes.
Journal of Applied Clinical Medical Physics 01/2012; 13(4):3753. · 1.29 Impact Factor
-
Amira Shakam,
Rufus Scrimger,
Derek Liu,
Mohamed Mohamed, Matthew Parliament,
G Colin Field,
Ali El-Gayed,
Pat Cadman,
Naresh Jha,
Heather Warkentin,
David Skarsgard,
Qiaohao Zhu,
Sunita Ghosh
[show abstract]
[hide abstract]
ABSTRACT: Although IMRT for head and neck cancer is widely accepted, the implications of sparing normal tissue immediately adjacent to target volumes are not well known.
Between 2002 and 2007, 124 patients with head and neck cancer were treated with surgery and postoperative IMRT (n=79) or definitive RT (n=45). Locoregional recurrences were analyzed for location relative to target volumes, and dosimetry.
With a median follow-up of 26.1months, a total of 16 locoregional recurrences were observed. The five-year actuarial locoregional disease-free survival was 82% [95% CI, 72-90%]. Analysis of 18 distinct sites of locoregional failure revealed that five of these failures were within the high dose clinical target volume (CTV), nine failures were at the margin of the CTV, and four recurrences were outside the CTV. The mean dose delivered to these recurrent volumes was 63.1 Gy [range: 57-68 Gy], while the mean dose to the coolest 1cc within each recurrence was 60.0 Gy [range: 51-67 Gy]. There were two periparotid recurrences observed.
We observed excellent locoregional control rates overall. The majority of recurrences occur within high dose regions of the neck and not near the spared parotid glands.
Radiotherapy and Oncology 05/2011; 99(2):101-7. · 5.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Biomarkers are of interest for predicting or monitoring normal tissue toxicity of radiation therapy. Advances in molecular radiobiology provide novel leads in the search for normal tissue biomarkers with sufficient sensitivity and specificity to become clinically useful. This article reviews examples of studies of biomarkers as predictive markers, as response markers, or as surrogate endpoints for radiation side effects. Single nucleotide polymorphisms are briefly discussed in the context of candidate gene and genomewide association studies. The importance of adjusting for radiation dose distribution in normal tissue biomarker studies is underlined. Finally, research priorities in this field are identified and discussed.
International journal of radiation oncology, biology, physics 03/2010; 76(3 Suppl):S145-50. · 4.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our aim was to evaluate the prevalence and relationship of symptoms with reduced dietary intake, weight, and functional capacity in patients with head and neck cancer.
Three hundred forty-one patients were prospectively screened with the patient-generated subjective global assessment before treatment. Logistic analysis was used to relate symptoms to reduced dietary intake, weight, and functional capacity. Cumulative hazard analysis was performed to determine the time and risk of weight loss of each symptom. Survival analysis was performed with Cox proportional hazards model.
Anorexia, dysphagia, mouth sores, and others were significant predictors of reduced dietary intake and weight. Symptom presence accelerated the time and probability of weight loss. Body mass index < or = 18.5 related to overall survival (p value = .001).
Symptoms present before treatment may adversely affect the dietary intake, weight, and functional capacity of patients. Symptom treatment and management is critical to weight loss prevention.
Head & Neck 08/2009; 32(3):290-300. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nodal dissection of the neck is often performed in conjunction with surgical resection of the primary tumour site for head and neck cancers. A major complication of neck dissection procedures is loss of trapezius muscle function due to temporary damage to, or resection of, the spinal accessory nerve. Over time, the resulting shoulder dysfunction may deteriorate to a chronic state that includes glenohumeral joint restriction and marked deformity of the shoulder complex. Patients with severe discomfort may require long-term use of narcotic analgesics. Although successful outcomes from physiotherapy have been reported in the literature for over 20 years, research in the area is sparse and uncertainty remains over the most effective therapeutic interventions. We present 3 case reports that illustrate the beneficial role of progressive resistance exercise training (PRET) to alleviate shoulder pain and dysfunction in head and neck cancer patients with spinal accessory nerve damage.
07/2009; 20(1):41-56.
-
[show abstract]
[hide abstract]
ABSTRACT: To quantify daily bladder size and position variations during bladder cancer radiotherapy.
Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions.
A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, -0.32 cm). The anterior bladder wall shifted the most (mean, -0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (+/- standard deviation [SD]) outside the planning CT counterpart was 29.24 cm(3) (SD, 29.71 cm(3)). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm(3) (SD, 21.64 cm(3)). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm(3) (SD, 36.51 cm(3)). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm(3) (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm(3) (SD, 3.97 cm(3)). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047).
Significant variations in bladder and PTV volume and position occurred in patients in this trial.
International journal of radiation oncology, biology, physics 07/2009; 76(4):1045-53. · 4.59 Impact Factor
-
Nadeem Pervez,
Cormac Small,
Marc MacKenzie,
Don Yee, Matthew Parliament,
Sunita Ghosh,
Alina Mihai,
John Amanie,
Albert Murtha,
Colin Field,
David Murray,
Gino Fallone,
Robert Pearcey
[show abstract]
[hide abstract]
ABSTRACT: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients.
Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of > or =T3a or an initial prostate-specific antigen [PSA] level of > or =20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales.
All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity.
Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.
International journal of radiation oncology, biology, physics 04/2009; 76(1):57-64. · 4.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to survey the use of reirradiation (Re-RT) for in-field failures after previous radical radiation treatment (RT) among Canadian radiation oncologists (ROs).
An electronic survey was sent to 271 ROs in Canada. The completed surveys were received electronically via e-mail and the data were analyzed using SAS 9.1.3 software.
A total of 183 ROs (67.5%) completed and returned the survey. The majority of the respondents were involved in the practice of either breast (48%) or genitourinary (43%) tumor sites. A total of 49% of the participants were interested in using Re-RT for the management of in-field recurrences. The goals of the therapy would be improvement of quality of life (99%), locoregional control (80%), or cure (32%). Most of the physicians believed that patients should have a minimum Karnofsky performance status of 50 or Eastern Cooperative Oncology Group performance status of 3, a minimum life expectancy of 3 months, and a minimum interval from initial treatment of 3 months if Re-RT were to be given with curative intent.
This survey showed that a wide variation existed among ROs in their approach to Re-RT. Newer technologies in RT planning and delivery would be employed to facilitate normal tissue avoidance. The results of this study suggested that a consensus meeting was needed to establish guidelines for the practice and prospective evaluation of Re-RT.
International journal of radiation oncology, biology, physics 06/2008; 72(5):1523-9. · 4.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the strength of correlation between measured saliva flow rates and various toxicity endpoints commonly used in head and neck cancer (HNC) treatment.
All patients enrolled in a phase II study using intensity modulated radiotherapy (IMRT) for HNC treatment underwent whole mouth saliva flow measurements (stimulated and unstimulated). They were also assessed for salivary gland toxicity using Radiation Therapy Oncology Group (RTOG) late toxicity grading and 9 items representing patient-graded toxicities from 2 questionnaires (Xerostomia questionnaire and University of Washington quality of life). For each patient, saliva flow rates and quality of life (QOL) data were collected preradiotherapy (RT) and at 3 intervals post-RT (3, 6, and 12 months).
A total of 188 sets of coregistered data were obtained for 47 patients over a period of approximately 4 years. Saliva production and mean QOL dropped significantly immediately after RT, but there was a statistically significant recovery in both parameters between 3- and 12-month post-RT. By 12 months, post-RT the mean QOL scores had returned to pre-RT baseline, although mean stimulated saliva production remained 58% below baseline.
Patients with HNC treated with IMRT experienced a small drop in QOL which recovered to baseline by 12 months post-RT. There was no statistically significant correlation seen between global health-related QOL scores and stimulated saliva production rates in the post-RT period.
American journal of clinical oncology 07/2007; 30(3):271-7. · 2.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Physical exercise training has been shown to be an effective component of comprehensive rehabilitation for some cancer patients and survivors. The purpose of this paper is to review the potential role of exercise training in the clinical setting and examine methods to deliver these services in the clinical setting. Noting the limited direct research on implementation of clinical exercise programs in the cancer setting, we review the literature and propose guidelines for: 1) goals of the prescribed physical activity or exercise program; 2) medical and pre-exercise evaluations; 3) recommendations for exercise programming; 4) safety considerations; 5) barriers to physical activity and exercise training in cancer patients; 6) self-directed and community based exercise programs; and 7) the role of medical and exercise professionals.
Current Cancer Therapy Reviews 10/2006; 2(4):351-360.
-
Sambasivarao Damaraju,
David Murray,
Jennifer Dufour,
Diana Carandang,
Sten Myrehaug,
Gino Fallone,
Colin Field,
Russell Greiner,
John Hanson,
Carol E Cass, Matthew Parliament
[show abstract]
[hide abstract]
ABSTRACT: To explore the possible relationship between single nucleotide polymorphisms (SNP) in candidate genes encoding DNA damage recognition/repair/response and steroid metabolism proteins with respect to clinical radiation toxicity in a retrospective cohort of patients previously treated with three-dimensional conformal radiotherapy (3-DCRT) for prostate cancer.
One hundred twenty-four patients with prostate cancer underwent 3-DCRT at our institution between September 1996 and December 2000. Of these, 83 consented for follow-up of blood sampling and SNP analysis. Twenty-eight patients were documented as having experienced grade >/=2 late bladder or rectal toxicity (scoring system of Radiation Therapy Oncology Group) on at least one follow-up visit. We analyzed 49 SNPs in BRCA1, BRCA2, ESR1, XRCC1, XRCC2, XRCC3, NBN, RAD51, RAD52, LIG4, ATM, BCL2, TGFB1, MSH6, ERCC2, XPF, NR3C1, CYP1A1, CYP2C9, CYP2C19, CYP3A5, CYP2D6, CYP11B2, and CYP17A1 genes using the Pyrosequencing technique.
Significant univariate associations with late rectal or bladder toxicity (grade >/=2) were found for XRCC3 (A>G 5' untranslated region NT 4541), LIG4 (T>C Asp(568)Asp), MLH1 (C>T, Val(219)Ile), CYP2D6*4 (G>A splicing defect), mean rectal and bladder dose, dose to 30% of rectum or bladder, and age <60 years. On Cox multivariate analysis, significant associations with toxicity were found for LIG4 (T>C, Asp(568)Asp), ERCC2 (G>A, Asp(711)Asp), CYP2D6*4 (G>A, splicing defect), mean bladder dose >60 Gy, and dose to 30% of rectal volume >75 Gy.
In this study, we identified SNPs in LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk for complications arising from radiation therapy in prostate cancer.
Clinical Cancer Research 05/2006; 12(8):2545-54. · 7.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This is the first report of toxicity outcomes at dose Level V (78 Gy) on Radiation Therapy Oncology Group 9406 for Stages T1-T2 adenocarcinoma of the prostate.
A total of 225 patients were entered in this cooperative group, Phase I-II dose-escalation trial of three-dimensional conformal radiotherapy for localized carcinoma of the prostate treated to a dose of 78 Gy (Level V). Of these patients, 219 were analyzed for acute and 218 for late toxicity. A minimum of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion as determined by Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stages T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stages T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 78 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 78 Gy. PTV margins of between 5 and 10 mm were required. The average time at risk for late Grade 3+ toxicity after therapy completion was 23.2 and 23.1 months for Groups 1 and 2, respectively. The frequency of Grade 3 or worse late effects was compared with a similar group of patients treated in Radiation Therapy Oncology Group (RTOG) studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 170 patients treated to dose Level III (79.2 Gy in 1.8 Gy/fraction) to see whether the fraction size affected toxicity. Unlike other dose levels, patients treated at dose Level III had treatment prescribed as a minimum to the gross tumor volume. This effectively lowered the volume of the rectum treated to the study dose.
Acute toxicity at dose Level V (78 Gy) was remarkably low, with Grade 3 acute effects reported in only 4% of Group 1 and 2% of Group 2 patients. No Grade 4 or 5 acute toxicity was reported. There was no statistically significant difference in rates of acute toxicities in patients who were treated to 79.2 Gy at 1.8 Gy/fraction or 78 Gy at 2.0 Gy/fraction. Late toxicity continues to be low compared with RTOG historical controls. The observed rate of Grade 3 or worse late effects for Group 1 (6 cases) was significantly lower (p = 0.0042) than the 18.2 cases that would have been expected from the historical control. The observed rate for Group 2 (8 cases) was lower than the 15.5 cases expected, but this difference was not statistically significant (p = 0.06). A trend was noted that Group 2 patients treated on dose Level V had more late Grade 3 or worse toxicity than patients treated to a similar dose on Level III (7% vs. 1%, p = 0.06). A significantly (p < 0.0001) greater incidence of late Grade 2 or greater toxicity occurred in patients treated at dose Level V (30% and 33% for Groups 1 and 2, respectively) than at dose Level III (13% and 9% for Groups 1 and 2, respectively). The longer follow-up at dose Level III suggests these differences may increase with additional follow-up.
Tolerance to three-dimensional conformal radiotherapy with 78 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size and treatment volume requires additional follow-up.
International Journal of Radiation OncologyBiologyPhysics 08/2005; 62(3):706-13. · 4.11 Impact Factor
-
Arnab Chakravarti,
Kathryn Winter,
Chin-Lee Wu,
Donald Kaufman,
Elizabeth Hammond, Matthew Parliament,
William Tester,
Michael Hagan,
David Grignon,
Niall Heney,
Alan Pollack,
Howard Sandler,
William Shipley
[show abstract]
[hide abstract]
ABSTRACT: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706).
Tumors from 73 cases from patients with muscle-invading T2-T4a bladder cancers had slides interpretable for EGFR staining; 55 cases had slides interpretable for Her-2 staining. Additionally, the respective prognostic values of p53, pRB, and p16 immunostaining were concomitantly examined. Staining and interpretation of staining were done in a blinded manner, without knowledge of clinical outcome. Staining was judged as positive or negative. Subsequently, staining was correlated with clinical outcome.
On univariate analysis, EGFR positivity was significantly associated with improved overall survival (p = 0.044); disease-specific survival (DSS) (p = 0.042); and DSS with intact bladder (p = 0.021). There was also a trend for association between EGFR expression and reduced frequency of distant metastasis (p = 0.06). On multivariate analysis adding tumor stage, tumor grade, whether a visibly complete transurethral resection of bladder tumor (TURBT) was done or not, and patient age to the model, EGFR positivity was significantly associated with improved DSS. On univariate analysis, Her-2 positivity was significantly associated with reduced complete response (CR) rates (50% vs. 81%, p = 0.026) after chemoradiation which remained significant on multivariate analysis. The other markers examined in this study were not found to have any prognostic value in this setting.
Epidermal growth factor receptor expression appears to correlate significantly with improved outcome in bladder cancer, whereas Her-2 expression is significantly associated only with reduced CR rates after chemoradiation. Further investigations are warranted into how EGFR family members regulate response to chemoradiation in bladder cancer and their potential therapeutic implications.
International Journal of Radiation OncologyBiologyPhysics 07/2005; 62(2):309-17. · 4.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypoxia-tolerant human glioma cells reduce oxygen consumption rate in response to oxygen deficit, a defense mechanism that contributes to survival under moderately hypoxic conditions. In contrast, hypoxia-sensitive cells lack this ability. As it has been previously shown that hypoxia-tolerant (M006x, M006xLo, M059K) and -sensitive (M010b) glioma cells express differences in mitochondrial function, we investigated whether mitochondrial DNA-encoded mutations are associated with differences in the initial response to oxygen deficit.
The mitochondrial genome was sequenced and 23 mtDNA alterations were identified, one of which was an unreported mutation (T-C transition in base pair 14634) in the hypoxia-sensitive cell line, M010b, that resulted in a single amino acid change in the gene encoding the ND6 subunit of NADH:ubiquinone oxidoreductase (Complex I). The T14634C mutation did not abrogate ND6 protein expression, however, M010b cells were more resistant to rotenone, an agent used to screen for Complex I mutations, and adriamycin, an agent activated by redox cycling. The specific function of mtDNA-encoded, membrane-embedded Complex I ND subunits is not known at present. Current models suggest that the transmembrane arm of Complex I may serve as a conformationally driven proton channel. As cellular respiration is regulated, in part, by proton flux, we used homology-based modeling and computational molecular biology to predict the 3D structure of the wild type and mutated ND6 proteins. These models predict that the T14634C mutation alters the structure and orientation of the trans-membrane helices of the ND6 protein.
Complex I ND subunits are mutational hot spots in tumor mtDNA. Genetic changes that alter Complex I structure and function may alter a cell's ability to respond to oxygen deficit and consolidate hypoxia rescue mechanisms, and may contribute to resistance to chemotherapeutic agents that require redox cycling for activation.
Molecular Cancer 08/2004; 3:19. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Shoulder dysfunction remains a frequent complication after neck dissection procedures for head and neck cancer.
We conducted a pilot study to evaluate the effects of progressive resistance exercise training (PRET) on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in patients with head and neck cancer. Twenty patients (mean age, 61 +/- 7.7 years) were randomly assigned to PRET or standard care intervention. Subjects assigned to the PRET group exercised three times per week for 12 weeks. The goal of the exercise program was to enhance scapular stability and strength of the upper extremity. The resistance-training program was progressive in terms of number of sets and repetitions performed, as well as the amount of weight lifted, depending on performance status.
The completion rate for the trial was 85% (17 of 20). The exercise group completed 93% of scheduled exercise sessions. Significant improvements were found in favor of the PRET group in active shoulder external rotation (p =.001), shoulder pain (p =.038), and overall score for shoulder pain and disability (p =.045).
The study results demonstrate a high rate of completion and adherence with our PRET program among patients with head and neck cancer. The preliminary findings, although limited, also suggest a potential therapeutic role for resistance exercise as an adjunct to standard physical therapy treatment.
Head & Neck 07/2004; 26(6):518-30. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Three hundred Canadian primary care physicians were surveyed to determine their perceived barriers to the accessibility of palliative bone radiotherapy and their perceptions regarding treatment efficacy. The response rate was 61%. Factors perceived to hinder accessibility were identified, and the physicians recognized they were not comfortable with their radiotherapy knowledge.
Radiotherapy and Oncology 06/2003; 67(2):221-3. · 5.58 Impact Factor
