Mathias Bressel

18F-FDG PET/CT Has a High Impact on Patient Management and Provides Powerful Prognostic Stratification in the Primary Staging of Esophageal Cancer: A Prospective Study with Mature Survival Data

The aim of this study is to evaluate the incremental staging information, management impact, and prognostic stratification of PET/CT in the primary staging of esophageal cancer in a cohort of patients with mature survival data. Methods: Between July 2002 and June 2005, 139 consecutive patients with newly diagnosed esophageal cancer underwent conventional staging investigations (CSI), followed by PET/CT. Disease stage was classified according to the American Joint Committee on Cancer staging system (6th edition) and grouped as stage I–IIA, stage IIB–III, and stage IV reflecting broad groupings that determine therapeutic choice. Validation of results was performed when PET/CT and CSI stage groups were discordant and in those patients where PET/CT changed management. Management impact was determined by comparing prospectively recorded pre-PET/CT management plans with post-PET/CT management plans. Survival after follow-up of at least 5 y in patients was analyzed using the Kaplan–Meier product limit method and the Cox proportional hazards regression model. Results: PET/CT changed the stage group in 56 of 139 (40%) patients and changed management in 47 of 139 (34%) patients. In 22 patients, therapy was changed from curative to palliative and in 3 from palliative to curative; in 11, treatment modality was changed without a change in treatment intent, and in 11 the delivery of therapy or diagnostic procedure was changed. Of the 47 patients with management change, imaging results could be validated in 31 patients, and PET/CT correctly changed management in 26 (84%) of these. Of the remaining 5 patients, CSI stage was also incorrect in 4 and correct in 1. Median survival was 23 mo. PET/CT stages I–IIA, IIB–III, and IV had a 5-y survival of 40%, 38%, and 6%, respectively. Post-PET/CT stage group and treatment intent were both strongly associated with survival (P < 0.001). Conclusion: PET/CT provides incremental staging information compared with CSI, changes management in one third of patients, and has powerful prognostic stratification in the primary staging of esophageal cancer.

18F-FDG PET Provides High-Impact and Powerful Prognostic Stratification in the Staging of Merkel Cell Carcinoma: A 15-Year Institutional Experience

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited evidence on the role of PET scanning. The primary aim of this study was to assess the impact of 18F-FDG PET in the staging and management of MCC. Methods: A single-institution review using clinical outcome data collected until February 2012 was performed of patients with MCC who underwent staging PET scanning between January 1997 and October 2010. Management plans were recorded prospectively at the time of the PET request, and follow-up outcomes were recorded retrospectively. The clinical impact of PET was scored using our previously published criteria: “high” if the PET scan changed the primary treatment modality or intent; “medium” if the treatment modality was unchanged but the radiation therapy technique or dose was altered. The primary objective was to test the hypothesis that the true proportion of patients who have a high- or medium-impact scan would be greater than 25%. Results: The median follow-up of 102 consecutive patients was 4.8 y. The results of staging PET had an impact on patient management in 37% of patients (P < 0.003). High- and medium-impact scans were recorded for 22% and 15% of patients, respectively. PET staging results differed from conventional staging results in 22% of patients, with PET upstaging 17% and downstaging 5%. The 3- and 5-y overall survival was 60% (95% confidence interval, 50%–71%) and 51% (95% confidence interval, 41%–64%), respectively. In stratification by PET-defined stage, the 5-y overall survival was 67% for patients with stage I/II disease but only 31% for patients with stage III disease (log-rank P < 0.001). The 5-y cumulative incidence of locoregional failure, distant failure, and death was 16.6%, 22.3% and 14.3%, respectively. On multivariate analysis, only PET stage (P < 0.001) and primary treatment modality (P = 0.050) were significantly associated with overall survival. The primary treatment modality was not associated with progression-free survival when stratification was by tumor stage. Conclusion: The use of 18F-FDG PET scans had a great impact on patients and may play an important role in the prognostic stratification and treatment of this disease.

Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy

For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non‐small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside (18F‐FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation.

Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective, multi-centre, International Extranodal Lymphoma Study Group study

BACKGROUND We evaluated the long-term results of radiotherapy for patients with gastric marginal zone lymphoma (GMZL). PATIENTS AND METHODS We carried out a retrospective, multi-centre study of patients with low-grade GMZL treated by radiotherapy between 17 July 1981 and 25 March 2004. RESULTS There were 102 eligible patients. Fifty-eight patients were previously untreated and 44 had recurrent/residual disease after prior treatment (HP eradication, chemotherapy and surgery in 35, 9 and 8 patients, respectively, and 7 had >1 prior therapy). Radiation fields included the stomach /involved nodes in 61 patients and whole abdomen in 41. The median radiotherapy dose to stomach was 40 Gy (range 26-46 Gy) in a median 22 fractions. With a median follow-up after radiotherapy of 7.9 years (range 0.3-24 years), 10- and 15-year freedom from treatment failure (FFTF) was 88% (95% CI 82%-95%). Risk factors for TF were a large-cell component (P = 0.036) and an exophytic growth pattern (P = 0.042). Radiotherapy field size, radiotherapy dose, and failure of prior therapy were not associated with inferior FFTF. Ten-year overall survival was 70% (95% CI 60%-82%). CONCLUSIONS Radiotherapy achieves cure for the majority of patients with low-grade GMZL, including patients who have had prior therapy. Several features may predict a poorer outcome.

Late toxicity and biochemical control in 554 prostate cancer patients treated with and without dose escalated image guided radiotherapy.

BACKGROUND AND PURPOSE To compare rates of late gastrointestinal toxicity, late genitourinary toxicity and biochemical failure between patients treated for prostate cancer with implanted fiducial marker image guided radiotherapy (FMIGRT), and those treated without FMIGRT. METHODS AND MATERIALS We performed a single institution retrospective study comparing all 311 patients who received 74 Gy without fiducial markers in 2006 versus all 243 patients who received our updated regimen of 78 Gy with FMIGRT in 2008. Patient records were reviewed 27 months after completing radiotherapy. Biochemical failure was defined using the Phoenix definition. Details of late gastrointestinal and genitourinary toxicities were graded according to CTCAEv4. Moderate/severe toxicity was defined as a grade 2 or higher toxicity. Cumulative incidence and prevalence curves for moderate/severe toxicity were constructed and compared using multistate modeling while biochemical failure free survival was compared using the log rank test. A Cox regression model was developed to correct for confounding factors. RESULTS Median follow-up time for both groups was 22 months. The hazard ratio for moderate/severe late gastrointestinal toxicity in the non-FMIGRT group was 3.66 [95% CI (1.63-8.23), p=0.003] compared to patients in the FMIGRT group. There was no difference in the hazard ratio of moderate/severe late genitourinary toxicity between the two groups (0.44 [95% CI (0.19-1.00)]), but patients treated with FMIGRT did have a quicker recovery from their genitourinary toxicities HR=0.24 [95% CI (0.10-0.59)]. We were unable to detect any differences in biochemical failure free survival between the cohorts HR=0.60 [95% CI (0.30-1.20), p=0.143]. CONCLUSION Despite dose escalation, the use of FMIGRT in radical radiotherapy for prostate cancer significantly reduces the incidence of gastrointestinal toxicity and the duration of late genitourinary toxicity when compared to conventional non-FMIGRT techniques.

The use of fused PET/CT images for patient selection and radical radiotherapy target volume definition in patients with non-small cell lung cancer: Results of a prospective study with mature survival data

BACKGROUND AND PURPOSE This prospective study investigated the impact of radiotherapy (RT)-planning FDG-PET/CT on management of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Patients still eligible for radical RT after conventional staging underwent RT-planning PET/CT and, if disease was still treatable to 60 Gy, they entered our planning study, where visually-contoured tumour volumes derived with and without PET information were compared. If PET/CT detected advanced disease, palliative therapy was given. Overall survival (OS) for palliative and curative patients was compared. RESULTS Of 76 eligible patients, only 50 (66%) received radical chemoRT after PET/CT while 26 (34%) received palliative therapies because PET/CT detected advanced disease. Without PET, FDG-avid tumour would reside outside the planning target volume (PTV) in 36% of radical cases and in 25% <90% of the PTV would have received >95% prescribed dose. OS for all patients was 56.8% and 24.9% at 1 and 4 years, respectively. OS for patients given chemoRT was 77.5% and 35.6% at 1 and 4 years, respectively and was 32% for stage IIIA patients at 4 years. OS for patients treated palliatively was inferior (P<0.001); 16.3% and 4.1% at 1 and 4 years, respectively. CONCLUSIONS Planning PET/CT frequently changed management and was associated with excellent survival. Survival data from this study were presented in part at the 2011 World Lung Cancer Conference, Amsterdam and planning data at the 2010 Annual Scientific Meeting of the American Society for Therapeutic Radiology and Oncology, Chicago.

Patient-reported complications from fiducial marker implantation for prostate image-guided radiotherapy

OBJECTIVES To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy. METHODS 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale. RESULTS Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5). CONCLUSION Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS).

OBJECTIVES Obesity is an increasing health problem that is reported to influence chemotherapy dosing. The extent to which this occurs and whether this affects outcomes in ovarian cancer was unclear. To describe chemotherapy dosing practices in normal, overweight and obese patients treated for FIGO Stage III/IV serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS). To evaluate the relationship between body mass index (BMI), dose intensity of chemotherapy received, overall survival (OS) and progression free survival (PFS). METHODS Patient characteristics including age, height, weight, FIGO stage, serum creatinine, primary chemotherapy received and outcome data were extracted from medical records and entered into the AOCS database. Outcomes were analysed against BMI and relative dose intensity (RDI) received, based on calculations derived from a standard regimen (carboplatin AUC 5 and paclitaxel 175mg/m(2)). RESULTS 333 women were included in the analysis. 27% were overweight and 21% were obese. In cycle 1 66% of obese patients received carboplatin doses more than 5% below their optimal calculated dose, and 32% received sub-optimal paclitaxel doses, compared to 25% and 13% of normal weight patients respectively. Obese women were more likely to have received <85% RDI for carboplatin compared to normal weight women (p<0.001). BMI group and RDI of carboplatin and paclitaxel were not predictors of OS. Women who received less than 85% RDI for carboplatin had a worse PFS (univariate analysis, median PFS 11 versus 15 months; p=0.04). There was no significant association between RDI and OS or PFS in multivariate analysis. CONCLUSIONS Obesity is common in ovarian cancer patients, and commonly results in lower chemotherapy dosing than recommended. Analysis of chemotherapy dosing from this study suggests that reduced dose intensity of carboplatin, which was more common in obese women, may impact on PFS in patients with advanced serous ovarian cancer.

Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities.

Background:Cancer of unknown primary (CUP) is the fourth most common cause of cancer death. With advanced diagnostics and treatments, we investigated the proportion of cancers diagnosed as CUP, treatment outcomes and association with socioeconomic disparities.Methods:We analysed trends in CUP diagnosis and outcome within the Surveillance, Epidemiology, and End Results registry between 1973 and 2008.Results:The percentage of all cancers diagnosed as CUP has decreased over time comprising <2% of cancers since 2007. A higher proportion of CUP was diagnosed in the elderly, females, blacks and residents of less affluent or less educated counties. Median survival of all CUP patients was 3 months, with no improvement over time. The 5-year survival significantly improved in those with squamous histology (squamous cell carcinoma; SCC) but only marginally in non-SCC. Factors associated with a longer survival on multivariate analysis included white race; female; <65 years old; most recent decade at diagnosis; SCC; married; a histological diagnosis; and treatment with radiotherapy (all P<0.001). Despite the improvement in survival with radiotherapy, its use was less frequent in females and blacks.Conclusion:The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SCC CUP. However, significant socioeconomic disparities exist in diagnosis and survival, suggesting inequalities in access to diagnostic investigations and treatment.

Peripheral Blood CD34+ Cell Enumeration as a Predictor of Apheresis Yield: An Analysis of More Than 1,000 Collections

The role of the peripheral blood (PB) CD34(+) cell count in predicting the CD34(+) cell yield in hematopoietic progenitor cell apheresis collections is well established. However, sometimes unexpectedly poor CD34(+) cell yields are obtained. To determine the effect, if any, of a range of factors on the ability of the PB CD34(+) count to predict collection CD34(+) cell count, we performed a retrospective analysis on consecutive hematopoietic progenitor cell apheresis collections between 2004 and 2008. Factors investigated included mobilization regimen, PB white blood cell count, body weight, and disease. After exclusion of collections involving apheresis complications, a total of 1,225 PB CD34(+) cell results with corresponding collection CD34(+) cell results from 458 patients were analyzed. Although differences in the median PB CD34(+) cell counts and collection CD34(+) cell counts were seen between mobilized collections with chemotherapy plus granulocyte colony-stimulating factor and those with granulocyte colony-stimulating factor alone, the predictive capability of the PB CD34(+) cell count for the collection CD34(+) cell yield remained similar. Although poorer collection efficiencies were observed in the myelodysplastic syndrome/myeloproliferative disorder diagnostic subgroup, our findings confirm that PB CD34(+) cell analysis remains a powerful and irreplaceable tool for predicting hematopoietic progenitor cell apheresis CD34(+) cell yield.