Alvin Milner

CLINICAL IMPACT OF, AND PROGNOSTIC STRATIFICATION BY, F-18 FDG PET/CT IN HEAD AND NECK MUCOSAL SQUAMOUS CELL CARCINOMA

The aim of this study was to determine prospectively the incremental value of positron emission tomography/computed tomography (PET/CT) over conventional assessment (clinical examination and CT/MRI imaging).

Prospective study of percutaneous endoscopic gastrostomy tubes versus nasogastric tubes for enteral feeding in patients with head and neck cancer undergoing (chemo)radiation

Percutaneous endoscopic gastrostomy (PEG) tubes have largely replaced nasogastric tubes (NGTs) for nutritional support of patients with head and neck cancer undergoing curative (chemo) radiotherapy without any good scientific basis.

Randomized study of percutaneous endoscopic gastrostomy versus nasogastric tubes for enteral feeding in head and neck cancer patients treated with (chemo)radiation

Percutaneous endoscopic gastrostomy (PEG) tubes have largely replaced nasogastric tubes (NGT) for nutritional support of patients with head and neck cancer undergoing curative (chemo)radiotherapy without any good scientific basis. A randomized trial was conducted to compare PEG tubes and NGT in terms of nutritional outcomes, complications, patient satisfaction and cost. The study was closed early because of poor accrual, predominantly due to patients’ reluctance to be randomized. There were 33 patients eligible for analysis. Nutritional support with both tubes was good. There were no significant differences in overall complication rates, chest infection rates or in patients’ assessment of their overall quality of life. The cost of a PEG tube was 10 times that of an NGT. The duration of use of PEG tubes was significantly longer, a median 139 days compared with a median 66 days for NGT. We found no evidence to support the routine use of PEG tubes over NGT in this patient group.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy

Fludarabine combination chemotherapy achieves high response rates in chronic lymphocytic leukemia (CLL) and indolent lymphoma. The aim of this study was to investigate the incidence and characteristics of treatment-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) after treatment with fludarabine in combination for lymphoproliferative disorders and identify risk factors for its development. In all, 176 patients treated with fludarabine combination were followed for a median of 41 months (range 6–125 months). In all, 19 cases of t-MDS/AML have been identified for an overall rate of 10.8%. Median overall survival post-t-MDS/AML diagnosis was 11 months. Patients developing t-MDS/AML included 11/54 with follicular lymphoma (FL) (crude rate 20.4%), 5/82 with CLL (6.1%) and 3/24 with Waldenstrom macroglobulinemia or marginal zone lymphoma (12.5%). Most patients had other cytotoxic treatments (median 4, range 0–7) but three with FL had fludarabine combination as their only line of treatment. Of the eleven patients (6.3%) who received mitoxantrone with their first fludarabine combination, four (36.4%) developed t-MDS/AML (P=0.007). There was a trend toward prior cytotoxic therapy increasing the risk for t-MDS/AML (P=0.067). Fludarabine combination chemotherapy is associated with a moderate risk of t-MDS/AML particularly when combined with mitoxantrone. This complication should be considered when evaluating the potential benefit of this treatment in lymphoproliferative disorders.

The impact of 18-fluorodeoxyglucose positron emission tomography on the staging, management and outcome of anal cancer.

Accurate inguinal and pelvic nodal staging in anal cancer is important for the prognosis and planning of radiation fields. There is evidence for the role of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging and management of cancer, with early reports of an increasing role in outcome prognostication in a number of tumours. We aimed to determine the effect of FDG-PET on the nodal staging, radiotherapy planning and prognostication of patients with primary anal cancer. Sixty-one consecutive patients with anal cancer who were referred to a tertiary centre between August 1997 and November 2005 were staged with conventional imaging (CIm) (including computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound and chest X-ray) and by FDG-PET. The stage determined by CIm and the proposed management plan were prospectively recorded and changes in stage and management as a result of FDG-PET assessed. Patients were treated with a uniform radiotherapy technique and dose. The accuracy of changes and prognostication of FDG-PET were validated by subsequent clinical follow-up. Kaplan–Meier survival analysis was used to estimate survival for the whole cohort and by FDG-PET and CIm stage. The tumour-stage group was changed in 23% (14 out of 61) as a result of FDG-PET (15% up-staged, 8% down-staged). Fourteen percent of T1 patients (3 out of 22), 42% of T2 patients (10 out of 24) and 40% of T3–4 patients (6 out of 15) assessed using CIm, had a change in their nodal or metastatic stage following FDG-PET. Sensitivity for nodal regional disease by FDG-PET and CIm was 89% and 62%, respectively. The staging FDG-PET scan altered management intent in 3% (2 out of 61) and radiotherapy fields in 13% (8 out of 61). The estimated 5-year overall survival (OS) and progression-free survival (PFS) for the cohort were 77.3% (95% confidence interval (CI): 55.3–90.4%) and 72.2% (95% CI: 51.5–86.4%), respectively. The estimated 5-year PFS for FDG-PET and CIm staged N2-3 disease was 70% (95% CI: 42.8–87.9%) and 55.3% (95% CI: 23.3–83.4%), respectively. FDG-PET shows increased sensitivity over CIm for staging nodal disease in anal cancer and changes treatment intent or radiotherapy prescription in a significant proportion of patients.

The Impact of 18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography on the Staging and Management of Primary Rectal Cancer

Purpose18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has a role in recurrent colorectal cancer. This study was designed to assess the impact of PET-CT on management of primary rectal cancer.MethodsEighty-three patients with rectal cancer underwent PET-CT scan between 2002 and 2005. Referring physicians prospectively recorded stage and management plan after conventional imaging before PET-CT scan, which were compared to subsequent stage and management after PET-CT.ResultsStaging PET-CT caused a change in stage from conventional imaging in 26 patients (31 percent). Twelve (14 percent) were upstaged (7 change in N stage; 4 change in M stage; 1 change in N and M stage), and 14 (17 percent) were downstaged (10 change in N stage; 3 change in M stage; 1 change in N and M stage). PET-CT scan altered management intent in seven patients (8 percent) (curative to palliative 6 patients; palliative to curative 1 patient). Management was altered in ten patients (12 percent). There was no difference in impact with respect to tumor height.ConclusionsPET-CT scan impacts the management of patients with primary rectal cancer and influences staging/therapy in a third of patients and should be a component of rectal cancer workup.

Impact of point spread function reconstruction on thoracic lymph node staging with 18F-FDG PET/CT in non-small cell lung cancer.

Aim The aim of the present study was to evaluate the impact of point spread function (PSF) reconstruction on quantitative values and diagnostic accuracy of FDG PET/CT for nodal staging in non–small cell lung cancer. Patients and Methods Fifty-eight consecutive PET/CT examinations were reconstructed with both ordered subset expectation maximization (OSEM) and PSF algorithms. Two readers independently performed a randomized blinded review of PET/CT examinations and gave a nodal status (N0, N1, N2, or N3) to each PET data set. When discordant, a consensus was reached with a third reader. Sensitivity, specificity, positive and negative predictive values (NPV), and positive and negative likelihood ratios (LRs) were assessed and compared using a McNemar test. All PET data sets were then independently analyzed to extract quantitative PET values in 208 nodes and compare them using Bland-Altman analysis. Results Bland-Altman analysis showed that, on average, PSF reconstruction increased SUVmax, SUVmean, and node/background ratios by 48%, 28%, and 27%, respectively. This increase was more marked for nodes less than 1 cm than for nodes 1 cm or greater (P < 0.0001 for SUVmax, SUVmean, and node/background ratios). Point spread function PET had higher sensitivity (97%) and NPV (92%) than OSEM PET (78% and 57%, respectively; P = 0.01 and P = 0.04, respectively). Negative LR was 0.04 for PSF PET and 0.31 for OSEM PET. Conclusions By improving activity recovery, especially for nonenlarged nodes, PSF significantly improves the sensitivity, NPV, and negative LR of FDG-PET for nodal staging in non–small cell lung cancer. These data suggest that preoperative invasive nodal staging may be omitted in the case of a negative PSF FDG-PET/CT.

Effect of PET/CT on Management of Patients with Non–Small Cell Lung Cancer: Results of a Prospective Study with 5-Year Survival Data

We investigated the incremental management impact and prognostic value of staging with 18F-FDG PET/CT in patients with non–small cell lung cancer (NSCLC) being considered for potentially curative therapies. Methods: Information on 168 consecutive patients with NSCLC being considered for surgery or definitive radiotherapy with curative intent before PET/CT was entered into a prospective database. The pre-PET/CT management plan, based on conventional imaging (conventional CT, appropriately supplemented by bone scintigraphy or other modalities), was defined prospectively by referring clinicians before PET/CT results became available. After PET/CT, actual clinical management was recorded, and patients were followed up until 5 y or death. The appropriateness of PET/CT management plans was assessed by biopsy when available, clinical follow-up, and survival analysis. Results: Stage was discordant on PET/CT and conventional imaging in 50.6% of patients (41.1% upstaged, 9.5% downstaged), with high management impact (change in treatment modality or curative intent) in 42.3% of patients. Both conventional imaging stage and PET/CT stage were strongly predictive of overall survival (OS) but there were greater differences between hazard rates and separations in the OS curves for stage groupings determined using PET/CT. OS was also strongly predicted by PET/CT-directed choice of therapy (P < 0.0001). Conclusion: PET/CT frequently affects patient management and strongly predicts OS in NSCLC, supporting the appropriateness of such changes.

A Multicenter Phase II Trial of Thalidomide and Celecoxib for Patients with Relapsed and Refractory Multiple Myeloma

Preclinical data indicates that cyclooxygenase-2 (COX-2) inhibition impairs plasma cell growth and potentially synergizes with thalidomide. We performed a trial in previously treated patients with myeloma using thalidomide up to a maximum dose of 800 mg/d with celecoxib (400 mg bid). Outcomes were compared with a prior trial of thalidomide. Sixty-six patients with median age of 67 (range, 43-85) received a median dose of thalidomide and celecoxib of 400 and 800 mg/d, respectively, with median durations of treatment of 27 and 13 weeks, respectively. The most common toxicities associated with premature discontinuation of celecoxib (n = 30 of 53, 57%) were fluid retention and deterioration of renal function. Overall response rate (RR) was 42% and with 20 months median follow-up; the actuarial median progression-free survival and overall survival were 6.8 and 21.4 months, respectively. Unlike our prior study, age >65 years was not predictive of inferior RR due to improvement in RR in older patients with the combination (37% versus 15%, P = 0.08). The RR was superior in patients who received a total dose of celecoxib exceeding 40 g in the first 8 weeks of therapy (62% versus 30%, P = 0.021). Progression-free survival and overall survival were also improved. Other predictors for inferior progression-free survival were age >65 years (P = 0.016) and elevated β2-microglobulin (P = 0.017). This study provides evidence that the addition of high-dose celecoxib adds to the antimyeloma activity of thalidomide but this comes with unacceptable toxicity. Future studies should use newer COX-2 inhibitors with thalidomide, or their respective derivatives.

Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group.

PURPOSE The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. METHODS AND MATERIALS Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. RESULTS A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. CONCLUSIONS This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.