Ultra-late recurrences of gastro-intestinal carcinoma after primary resection: the mechanism of dormancy.

Curative resection of limited gastro-intestinal carcinoma does not always mean curation with tumor-free long-term survival. We present two cases of ultra-late recurrence 14 years after initial treatment. In the first case a 50-year-old male underwent in 1997 a subtotal esophagectomy with tubulation of the stomach for a localized Barrett carcinoma. Postoperative staging showed a poorly differentiated adenocarcinoma, pT1N1 (stage IIB). In May 2011, 14 years after the initial resection, multiple bone metastases were diagnosed and a biopsy confirmed the poorly differentiated carcinoma with the same characteristics as the primary tumor. Investigations showed no evidence for a new primary tumor. The second case is a 52-year old man who underwent a low anterior resection for a small rectal cancer in 1997, histologically a well differentiated adenocarcinoma, stage IB (pT2NO). In December 2011 multiple metastases were diagnosed and a biopsy showed a metastasis from a mucinous carcinoma, suggestive for a colorectal carcinoma. There was also no evidence for a new primary tumor. Although the prognosis of limited esophageal and colorectal cancer is good, recurrence is always possible and an ultra-late recurrence may exceptionally occur. The mechanism of tumor dormancy is described.

Non-Hodgkin lymphoma: retrospective study on the cost-effectiveness of early treatment response assessment by FDG-PET.

PURPOSE: Although lymphomas are very chemosensitive, 50% of patients with aggressive non-Hodgkin lymphoma (NHL) are not cured with standard first-line treatment. This consists of six cycles of doxorubicin, vincristine, prednisolone and cyclophosphamide (CHOP), recently complemented with rituximab. Preliminary studies show that PET mid-treatment is a good predictor of the remission status at the end of therapy. As patients with persistent FDG uptake after three cycles are unlikely to gain a complete remission, the remaining three cycles of chemotherapy are useless. We investigated the costs and benefits for the use of PET in this early treatment setting. METHODS: We conceived a model using a conventional arm where patients receive the full regimen of six cycles of CHOP [-rituximab] and an experimental algorithm where patients receive either six cycles (PET response) or only three cycles (PET non-response). Based on a patient sample (2004-2006), we calculated the costs for hospitalisation and treatment. We took into account all costs accrued (including overhead costs). We used a sensitivity analysis by varying the most important parameters. RESULTS: With a PET price of 700 euro and CHOP price (per cycle) of 1,829 euro , we can conclude to cost saving of 1,879 euro per patient. The PET price can increase up to 2,580 euro and the cost for one cycle of CHOP can decrease to 500 euro per cycle before cost savings are nil. The percentage of non-responders may be as low as 10%. The implementation of rituximab in first-line therapy only increases benefit (4,900 euro/pt). CONCLUSION: We conclude to substantial cost savings if management of NHL patients is based on mid-treatment PET scan. The economical data we used seem to be comparable to those published in other European studies. Implementation of Mabthera in first line only increases cost savings.

Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: Less than half of all patients with aggressive non-Hodgkin's lymphoma (NHL) are cured with standard chemotherapy. Therefore, it is important to distinguish between responders to standard treatment and non-responders who may benefit from an early change to a more effective therapy. This study was intended to assess the value of a midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) scan to predict clinical outcome in patients with aggressive NHL. PATIENTS AND METHODS: Seventy newly diagnosed patients with aggressive NHL, who were treated with doxorubicin-containing chemotherapy, underwent a [(18)F]FDG-PET scan at midtreatment. Presence or absence of abnormal [(18)F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Multivariate analysis was performed to evaluate the effect of the International Prognostic Index (IPI) and early [(18)F]FDG-PET findings on PFS and OS. RESULTS: At midtreatment, 33 patients showed persistent abnormal [(18)F]FDG uptake and none of these patients achieved a durable complete remission (CR), whereas 37 patients showed a negative scan; 31/37 remained in CR, with a median follow-up of 1107 days. Only 6/37 patients either achieved a partial response or relapsed. Comparison between groups indicated a statistically significant association between [(18)F]FDG-PET findings and PFS (P <1 x 10(-5)) and OS (P <1 x 10(-5)). In multivariate analysis, [(18)F]FDG-PET at midtreatment was a stronger prognostic factor for PFS (P <1 x 10(-7)) and OS (P <9 x 10(-6)) than the IPI (P <0.11 and P <0.03, respectively). CONCLUSIONS: Early restaging [(18)F]FDG-PET may be used to tailor induction chemotherapy in patients with aggressive NHL.

Can positron emission tomography with [(18)F]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin's disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity?

To assess the ability of restaging positron emission tomography (PET) scanning to predict clinical outcome after first-line treatment in patients with Hodgkin's disease, we included 60 patients with histologically proven HD, who underwent whole-body [(18)F]-fluorodeoxygenase ([(18)F]-FDG)-PET studies after first-line treatment and with a follow-up of at least 1 year. Persistence or absence of residual disease on PET was related to progression-free survival (PFS) using Kaplan-Meier survival analysis. After treatment, 55 patients showed a normal [(18)F]-FDG-PET scan; 50 of 55 remained in complete remission (CR), with a median follow-up of 955 d. Only five patients relapsed (median PFS, 296 d). During follow-up in all five patients, [(18)F]-FDG-PET was the first tool that became positive for relapse. Persistent abnormal [(18)F]-FDG uptake was seen in only five patients; all of them relapsed (median PFS, 296 d). In four of five patients, only PET predicted persistent disease. All relapses were proven histologically. Two-year actuarial PFS rate for negative patients was 91% compared with 0% for positive patients. We concluded that [(18)F]-FDG-PET has an important prognostic role in the post-treatment evaluation of HD patients.

Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods?

PURPOSE: A complete remission (CR) after first-line therapy is associated with longer progression-free survival (PFS). However, defining CR is not always easy because of the presence of residual masses. Metabolic imaging with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) offers the ability to differentiate between viable and fibrotic inactive tissue. In this study, we evaluated the value of PET in detecting residual disease and, hence, predicting relapse after first-line treatment in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Ninety-three patients with histologically proven NHL, who underwent a whole-body [18F]FDG-PET study after completion of first-line chemotherapy and who had follow-up of at least 1 year, were included. Persistence or absence of residual disease on PET was related to PFS using Kaplan-Meier survival analysis. RESULTS: Sixty-seven patients showed a normal PET scan after first-line chemotherapy; 56 of 67 remained in CR, with a median follow-up of 653 days. Nine of these patients with a residual mass considered as unconfirmed CR received additional radiotherapy. Only 11 of 67 patients relapsed (median PFS, 404 days). Persistent abnormal [18F]FDG uptake was seen in 26 patients, and all of them relapsed (median PFS, 73 days). Because standard restaging also suggested residual disease, 12 patients received immediate secondary treatment. In 14 of 26 patients, only PET predicted persistent disease. From these patients, relapse was proven either by biopsy (n = 8) or by progressive disease on computed tomography or magnetic resonance imaging (n = 6). CONCLUSION: Persistent abnormal [18F]FDG uptake after first-line chemotherapy in NHL is highly predictive for residual or recurrent disease. In relapsing patients, PFS was significantly shorter after a positive scan than after a negative scan.

Evaluation of treatment response in patients with lymphoma using [18F]FDG-PET: differences between non-Hodgkin's lymphoma and Hodgkin's disease.

Fluorine-18fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) has become a very useful technique for the therapy monitoring of patients with lymphoma. It provides unique information about the metabolic behavior of the disease independent of morphological criteria. In recent years, [18F]FDG-PET has proven to be a technique with high sensitivity for the detection of residual tumor. Therefore, [18F]FDG-PET seems to be the ideal tool for the evaluation of treatment response. However, most recent published studies included both HD and NHL, although [18F]FDG-PET scan results in Hodgkin's disease (HD) has a different impact than in Non Hodgkin's Lymphoma (NHL). In this paper, we summarize our findings on the role of [18F]FDG-PET in the therapy evaluation of lymphoma patients in a large group of patients and highlight the differences between the interpretations of the results of HD and NHL patients. Finally, a strategy for the implementation of [18F]FDG-PET in the management of lymphoma patients is proposed.