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Lester J Peters

Publications and source records attributed to Lester J Peters.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02.

PURPOSE: To determine the association between tumor hypoxia, treatment regimen, and locoregional failure (LRF) in patients with stage III or IV squamous cell carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35 fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and 7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional fluorouracil during weeks 6 and 7 (chemoboost). PATIENTS AND METHODS: Forty-five patients were enrolled onto a hypoxic imaging substudy of a larger randomized trial. Pretreatment and midtreatment [18F]-fluoromisonidazole positron emission tomography scans (FMISO-PET) were performed 2 hours after tracer administration, with qualitative scoring of uptake in both primary tumors and nodes. RESULTS: Thirty-two patients (71%) had detectable hypoxia in either or both primary and nodal disease. In patients who received chemoboost, one of 10 patients without hypoxia had LRF compared with eight of 13 patients with hypoxia; the risk of LRF was significantly higher in hypoxic patients (exact log-rank, P = .038; hazard ratio [HR] = 7.1). By contrast, in patients who received the TPZ/CIS regimen, only one of 19 patients with hypoxic tumors had LRF; risk of LRF was significantly higher in chemoboost patients (P = .001; HR = 15). Similarly, looking at the primary site alone, in patients with hypoxic primaries, zero of eight patients treated with TPZ/CIS experienced failure locally compared with six of nine patients treated with chemoboost (P = .011; HR = 0). CONCLUSION: Hypoxia on FMISO-PET imaging, in patients receiving a nontirapazamine-containing chemoradiotherapy regimen, is associated with a high risk of LRF. Our data provide the first clinical evidence to support the experimental observation that tirapazamine acts by specifically targeting hypoxic tumor cells.

Cell Hypoxia↗
PubMed2005

The 'QUAD SHOT'--a phase II study of palliative radiotherapy for incurable head and neck cancer.

BACKGROUND AND PURPOSE: The primary objective of this study was to estimate the rate of tumour response to a cyclical hypofractionated palliative radiotherapy regimen (QUAD SHOT) in previously untreated patients with incurable squamous cell carcinoma of the head and neck. Secondary objectives were to prospectively evaluate toxicity, quality of life (QoL) and survival in these patients. PATIENTS AND METHODS: The QUAD SHOT consisted of 14 Gy in four fractions, given twice a day and at least 6h apart, for 2 consecutive days. This regimen was repeated at 4 weekly intervals for a further two courses if there was no tumour progression. The QoL tool used was an abbreviation of the EORTC QLQ-C30. RESULTS: Thirty eligible patients (29 Stage IV, 20 performance status 2-3) had at least one treatment and 16 patients completed all three cycles. Sixteen patients (53%) had an objective response (2CR, 14PR) and a further seven had stable disease. Median overall survival was 5.7 months, median progression free survival was 3.1 months. The treatment was very well tolerated, with improved QoL in 11 of 25 evaluable patients (44%). CONCLUSION: The QUAD SHOT regimen is an effective palliative treatment with minimal toxicity and a good response rate, which impacts positively on patients' QoL.

Aged↗
PubMed2005

Relapse patterns in WHO 2/3 nasopharyngeal cancer: is there a difference between ethnic Asian vs. non-Asian patients?

PURPOSE: The purpose of this study was to assess whether ethnicity is an independent prognostic factor in patients with World Health Organization (WHO) type 2 or 3 nasopharyngeal carcinoma (NPC). Specifically, we examined the patterns of relapse observed in patients classified as "Asian" (born in southern China or southeast Asia) or "non-Asian" (born in Australia, Europe, the Middle East, or the Pacific Islands). METHODS AND MATERIALS: All patients planned for radical treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. Pathology was reviewed to confirm WHO type 2 or 3 NPC. Patients were staged using the 1997 International Union Against Cancer (UICC) criteria. Mean potential follow-up time was 9.6 years (range, 1.0-18.5 years) RESULTS: There were 158 patients: 86 Asian and 72 non-Asian. Stage groupings were: I--12 patients; II--32 patients; III--59 patients; and IV--55 patients. A staging computerized tomography was performed in 121 patients, and 53 (34%) also had a staging magnetic resonance imaging (MRI). The Asian patients had significantly more women, more patients aged <45, and more with performance status 0 than the non-Asians. Other putative prognostic factors were not significantly different between the groups. The 5-year rates for freedom from local recurrence (FLR), failure-free survival (FFS), and overall survival (OS) for Asian and non-Asian patients were 74% vs. 82%, 61% vs. 55%, and 75% vs. 63%, respectively. Corresponding 10-year figures were: 62% vs. 82%, 43% vs. 48%, and 58% vs. 49%, respectively. Multifactor analysis showed stage and the use of MRI for staging to be significant prognostic factors for all three endpoints. Age was also significant for FFS and OS. There were no significant differences in FFS or OS between Asian and non-Asian patients. However, the FLR interval was significantly worse in the Asian group (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.11-5.06), whereas duration of freedom from distant metastasis tended to be better (HR, 0.71; 95% CI, 0.33-1.53). CONCLUSIONS: Although this study provides no evidence that race is an independent prognostic factor for overall survival in patients with WHO 2/3 NPC, it does suggest that relapse patterns may vary, with a higher rate of late primary failures (offset by a lower rate of distant failure) in the Asian population. Further confirmatory studies with larger patient cohorts are indicated.

Adolescent↗
PubMed2005

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent.

PURPOSE: The purpose of the study was to evaluate [(18)F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. METHODS: Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [(18)F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. RESULTS: Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). CONCLUSION: The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer.

Adult↗
PubMed2005

Results of treatment intensification for progressive locoregional disease in head-and-neck cancer patients undergoing postoperative radiotherapy.

PURPOSE: Patients who develop progressive locoregional disease during radical surgery and postoperative radiotherapy for squamous cell carcinoma of the head and neck represent a management dilemma. We present our experience using treatment intensification for such patients. METHODS AND MATERIALS: A prospective record of eligible patients was kept between May 1998 and December 2001. The study included 15 patients, 11 men and 4 women (median age, 60 years); 67% had Stage III-IV disease. The sites of progression were primary in 3, nodes/scar in 10, and both primary and nodes in 2. Relative to the initial plan, treatment intensification was achieved by an increased radiation dose in 7 (using accelerated fractionation in 5), an increased radiation dose and the addition of concomitant chemotherapy in 7, and the addition of concomitant chemotherapy alone in 1 patient. RESULTS: The median follow-up was 40 months. Eight patients had a complete response to intensified treatment. At the closeout date, 6 patients were alive with no evidence of disease. Eight patients had died with locoregional disease; two also had distant metastases. One patient was lost to follow-up after achieving a complete response. The median failure-free survival for all patients was 6 months, but for those with a complete response, it was 37 months. The median overall survival time was 28 months. The 2-year and 3-year overall survival rate was 50% and 42%, respectively. Acute mucosal and skin toxicity was increased relative to standard postoperative radiotherapy but was not dissimilar to that expected after radical definitive chemoradiotherapy. CONCLUSION: Intensification of treatment in patients who develop progressive locoregional disease is warranted, because it can lead to long-term disease control in a subset of patients with significant but acceptable toxicity.

Aged↗
PubMed2005

Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer.

BACKGROUND: This study evaluates the utility of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with a node-positive mucosal head and neck squamous cell carcinoma who achieved a complete response at the primary site but had a residual mass in the neck 8 weeks or more after definitive (chemo)radiotherapy. METHODS: Between October 1996 and July 2002, 39 eligible patients were identified. The reference PET scan was performed at a median of 12 weeks (range, 8-32 weeks) after treatment. RESULTS: PET showed no metabolic activity in the residual mass in 32 patients. Five of these patients had a neck dissection and were all pathologically negative. The remaining 27 patients were observed for a median of 34 months (range, 16-86 months), with only one locoregional failure. The negative predictive value of PET for viable disease in a residual anatomic abnormality was 97%. CONCLUSION: Patients who have achieved a complete response at the primary site but have a residual abnormality in the neck that is PET negative approximately 12 weeks after treatment do not require neck dissection and can be safely observed. Head Neck

Adult↗
PubMed2004

Postoperative chemoradiotherapy for high-risk head-and-neck squamous cell carcinoma.

PURPOSE: To describe the use of postoperative concurrent chemoradiotherapy, with either weekly cisplatin or carboplatin, for high-risk head-and-neck squamous cell carcinoma (HNSCC) in a single institutional setting. METHODS AND MATERIALS: Between July 1999 and January 2003, 47 patients were treated with postoperative chemoradiotherapy. RESULTS: Of the 47 patients, 41 (87%) had Stage III-IV disease. The predominant primary site was the oral cavity in 24 patients (51%), 27 had nodal disease with extracapsular extension, and 26 had positive or close mucosal margins (<5 mm). Ten patients had undergone resection of recurrent disease after previous surgery. Twenty-seven (57%) were treated with cisplatin, and the remaining patients received carboplatin because of contraindications to cisplatin. The median radiotherapy dose was 60 Gy (range, 50-66 Gy). Of the 47 patients, 45 (96%) completed at least four of the six planned doses of chemotherapy and 45 (96%) completed the planned course of radiotherapy. Nineteen patients (40%) had confluent mucositis, eight (17%) had Grade 3-4 hematologic toxicity, and four (9%) had febrile neutropenia. No treatment-related deaths occurred. The estimated 2-year locoregional control, progression-free survival, and overall survival rate was 73%, 56%, and 62%, respectively. Excluding the 10 patients with recurrence after previous surgery, the locoregional control, progression-free survival, and overall survival rate was 81%, 64%, and 71%, respectively. Five cases of Grade 3-4 late treatment-related sequelae developed. CONCLUSION: Treatment with postoperative concurrent weekly cisplatin or carboplatin and radiotherapy was reasonably well tolerated. Acute and late toxicity was acceptable. The overall results achieved are comparable with the preliminary results of recent randomized trials. Patients treated after resection of recurrent disease (after previous surgery alone) fared worse than those treated at the initial resection.

Adult↗
PubMed2004

Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation.

PURPOSE: To investigate the relationship between positron emission tomography (PET) detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy for non-small-cell lung cancer. The prognostic significance of these changes was also studied. METHODS: In 73 consecutive patients, (18)F-fluorodeoxyglucose (FDG) PET was performed at a median of 70 days after completion of radical radiotherapy. Radiation-induced inflammatory change was scored for normal tissues within the radiation treatment volume using a 0-3 grading scale. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and posttreatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model. RESULTS: Increased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial tumor response on both PET (p = 0.0044) and computed tomography (p = 0.029). Prognostic stratification provided by PET response was both significant and of a similar magnitude in patients with low- and high-grade radiotoxicity. CONCLUSION: Postradiotherapy inflammatory changes detected by FDG-PET are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET is not compromised by inflammatory changes if a meticulous visual response assessment technique is used.

Adenocarcinoma↗
PubMed2004

Usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with a residual structural abnormality after definitive treatment for squamous cell carcinoma of the head and neck.

BACKGROUND: Residual structural abnormalities after definitive treatment of head and neck squamous cell carcinoma (HNSCC) are common and pose difficult management problems. The usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) to supplement conventional evaluation with clinical and standard radiologic examination (CE) in such patients was assessed. METHODS: Fifty-three eligible patients were identified with residual structural abnormalities on CE. True disease extent could be validated in 46 patients. Patients had a median potential follow-up of 55 months (range, 41-75 months) from the date of PET scan to the analysis closeout date. RESULTS: PET had better diagnostic accuracy than CE (p = .0002) and induced management change in 21 patients (40%; 95% confidence interval [CI], 26%-54%), including avoidance of unnecessary planned surgery in 14 patients with negative PET. Appropriate management change was confirmed in 19 (95%) of 20 evaluable cases. Disease presence and extent assessment by PET were significant predictors of survival (p < .0001), whereas the extent of disease determined by CE was not. CONCLUSION: PET added significantly to the value of CE in restaging disease in patients with structural abnormalities after definitive treatment of HNSCC. Management decisions based on PET were appropriate in most patients.

Aged↗
PubMed2004

Dosimetric study of optimal beam number and arrangement for treatment of nasopharyngeal carcinoma with intensity-modulated radiation therapy.

The purpose of this dosimetric study was to evaluate the effect of beam number and arrangement on the dose distribution with intensity-modulated radiation therapy in patients with nasopharyngeal cancer. Computed tomography data sets of seven patients who were treated for nasopharyngeal carcinoma at the Peter MacCallum Cancer Centre were used for the present dosimetric study. The dose planned was 70 Gy in 7 weeks for the gross nasopharyngeal and nodal disease and the biological equivalents of 60 Gy in 6 weeks for the high-risk and 50 Gy in 5 weeks for the low-risk nodal disease. A plan using seven fields was compared to that using nine fields in all patients. Plans were assessed on the dose to the planning target volume (PTV) and the degree of parotid sparing achieved by evaluating both dose-volume histograms (DVH) and axial slices. Seven fields (three anterior and four posterior) provide good PTV coverage and satisfactory parotid sparing in patients with localized nasopharyngeal lesions. Nine fields appear to be better for tumours with significant posterolateral parapharyngeal extension. Parotid sparing is consistently better with nine fields. Both DVH and axial slices need to be evaluated before accepting any plan.

Carcinoma↗
PubMed2004

'Boomerang' technique: an improved method for conformal treatment of locally advanced nasopharyngeal cancer.

The primary aim of the present study was to assess radiation dosimetry and subsequent clinical outcomes in patients with locally advanced nasopharyngeal cancer using a novel radiation technique termed the 'Boomerang'. Dosimetric comparisons were made with both conventional and intensity modulated radiation therapy (IMRT) techniques. This is a study of 22 patients treated with this technique from June 1995 to October 1998. The technique used entailed delivery of 36 Gy in 18 fractions via parallel opposed fields, then 24 Gy in 12 fractions via asymmetric rotating arc fields for a total of 60 Gy in 30 fractions. Patients also received induction and concurrent chemotherapy. The radiation dosimetry was excellent. Dose-volume histograms showed that with the arc fields, 90% of the planning target volume received 94% of the prescribed dose. Relative to other conventional radiation therapy off-cord techniques, the Boomerang technique results in a 27% greater proportion of the prescribed dose being received by 90% of the planning target volume. This translates into an overall 10% greater dose received for the same prescribed dose. At 3 years, the actuarial loco-regional control rate, the failure-free survival rate and the overall survival rate were 91, 75 and 91%, respectively. At 5 years, the actuarial loco-regional control rate, the failure-free survival rate and the overall survival rate were 74, 62 and 71%, respectively. The Boomerang technique provided excellent radiation dosimetry with correspondingly good loco-regional control rates (in conjunction with chemotherapy) and very acceptable acute and late toxicity profiles. Because treatment can be delivered with conventional standard treatment planning and delivery systems, it is a validated treatment option for centres that do not have the capability or capacity for IMRT. A derivative of the Boomerang technique, excluding the parallel opposed component, is now our standard for patients with locally advanced nasopharyngeal cancer when IMRT is not available.

Adolescent↗
PubMed2004

Outcomes in sinonasal mucosal melanoma.

BACKGROUND: The present paper assesses treatment outcomes in a series of 20 patients with sinonasal mucosal melanoma (SNMM) over 11 years. METHODS: All patients who presented to a single institution between 1991 and 2002 with a diagnosis of SNMM had their treatment reviewed and outcomes determined. RESULTS: Twenty patients presented to our institution with SNMM over the study period. No cervical node or metastatic involvement was detected at presentation. The most common site of involvement was the nasal cavity (17/20). The majority of patients received initial surgery followed by radiotherapy (15/20). At the completion of treatment 14 patients had no disease evident. The median time to failure in these patients was 12 months. Of these patients 10 relapsed, including six who had metastatic failure only. Fifteen patients died due to disease. Median overall survival was 17 months, with a 2-year overall survival of 23%. In univariate analysis, patients with advanced tumours (T3-4) had a 4.3 times greater risk of dying than patients with early tumours (T1-2). CONCLUSIONS: Patients with SNMM have poor outcomes with conventional therapy. Full staging prior to treatment is recommended. Aggressive treatment carrying significant morbidity is justified only for patients with early stage disease.

Aged↗
PubMed2003

The usefulness of fluorine 18-labelled deoxyglucose positron emission tomography in the investigation of patients with cervical lymphadenopathy from an unknown primary tumor.

BACKGROUND: The usefulness of fluorine 18-labelled deoxyglucose positron emission tomography (PET) in the detection of unknown primary tumor in patients seen with malignant cervical lymphadenopathy thought to arise from a head and neck primary differs in the published reports to date. To assess the role of PET in this scenario in our institution, an audit was performed. METHODS: The records of 21 patients who met the clinical indication were reviewed. End points were the ability of PET to detect an unknown primary tumor and/or distant metastatic disease. RESULTS: In 8 of the 21 patients, PET detected a potential primary site, although none was unequivocally PET positive. One case was pathologically confirmed. In five patients the potential primary site identified on PET could not be confirmed: two had negative biopsies, and three had no clinical evolution in the PET-suspect area for at least 24 months after the initial study. In the remaining two patients, the potential primary site detected by PET was treated without biopsy. PET detected additional regional and/or distant disease that had not been previously documented in nine cases. CONCLUSIONS: PET did not add significantly to the detection of an occult primary tumor in patients who had already been comprehensively evaluated by clinical and radiologic investigations. It was of substantial benefit, however, in detecting unsuspected distant disease in patients with undifferentiated nodal histologic findings and helped in delineating regional disease in patients with N2 disease.

Adult↗
PubMed2003

The effect of anaemia on efficacy and normal tissue toxicity following radiotherapy for locally advanced squamous cell carcinoma of the head and neck.

PURPOSE: The aims of this analysis were to determine the effect of anaemia on loco-regional control, relapse-free survival, cause-specific survival, overall survival, and acute and late radiation therapy toxicity in patients with Stage III and IV squamous cell carcinoma of the head and neck treated with radiotherapy. PATIENTS AND METHODS: Between 1991 and 1998, 350 patients were randomly assigned to either conventional radiotherapy, (70 Gy in 35 fractions in 49 days) or to accelerated radiotherapy (59.4 Gy in 33 fractions in 24 days). Patients were divided into two groups according to their haemoglobin level: a normal haemoglobin group (>/=13 g/dl in males, >/=12 g/dl in females) and a low haemoglobin group (<13 g/dl in males, <12 g/dl in females). The influence of anaemia on cause-specific survival and the development of confluent mucositis independent of other variables was tested using Cox proportional hazards model. RESULTS: Of 350 patients recruited to the trial, 238 had haemoglobin measurements and were eligible for inclusion in this secondary analysis. One hundred and ninety-three were considered to have normal haemoglobin, and 45 patients were considered to be anaemic. There were significant differences between the groups in loco-regional control, relapse-free survival, cause-specific survival and overall survival, with hazards ratios of 0.56 (95% confidence interval (CI) 0.34-0.94), 0.57 (95% CI 0.35-0.92), 0.49 (95% CI 0.29-0.85) and 0.43 (95% CI 0.26-0.70) in favour of the normal haemoglobin group. Using Cox proportional hazards modelling, haemoglobin level was a significant predictor of cause-specific survival in addition to disease site, stage, and Eastern Cooperative Oncology Group status. There were no statistically significant differences between the groups in the development of acute or late reactions. CONCLUSION: Significant reductions in loco-regional control, disease-free survival, cause-specific survival and overall survival occur in the presence of anaemia. No significant differences in normal tissue toxicity have been identified in this analysis.

Anemia↗
PubMed2002

Factors affecting risk of symptomatic temporal lobe necrosis: significance of fractional dose and treatment time.

PURPOSE: To study the factors affecting the risk of symptomatic temporal lobe necrosis after different fractionation schedules. METHODS AND MATERIALS: One thousand thirty-two patients with T1-2 nasopharyngeal carcinoma treated with radical radiotherapy in Hong Kong during 1990-1995 were studied. They were treated at four different centers with similar techniques but different fractionation schedules: 984 patients were given 1 fraction daily throughout (q.d.), and 48 patients were irradiated twice daily (b.i.d.) for part of the course. The median total dose was 62.5 Gy (range 50.4-71.2), dose per fraction was 2.5 Gy (range 1.6-4.2), and overall treatment time (OTT) was 44 days (range 29-70). In addition, 500 patients received supplementary doses for parapharyngeal extension, 113 received booster doses by brachytherapy, and 114 received sequential chemotherapy using cisplatin-based regimes. RESULTS: Altogether, 24 patients developed symptomatic temporal lobe necrosis: 18 from the q.d. group and 6 from the b.i.d. group. The 5-year actuarial incidence ranged from 0% (after 66 Gy in 33 fractions within 44 days) to 14% (after 71.2 Gy in 40 fractions within 35 days). Multivariate analyses showed that the risk was significantly affected by the fractional effect of the product of total dose and dose per fraction (hazard ratio [HR] = 1.04, 95% confidence interval [CI] 1.02-1.05), OTT (HR 0.88, 95% CI 0.80-0.97), and b.i.d. scheduling (HR 13, 95% CI 3-54). Repeating the analyses for patients treated with the q.d. schedules confirmed the independent significance of OTT in addition to the product of total dose and dose per fraction. CONCLUSION: The tentative results suggest that in addition to fractional dose, the OTT also had significant impact on the risk of temporal lobe necrosis, and b.i.d. scheduling increased the hazard further.

Adolescent↗