Risk-adapted FDG–PET/CT-based follow-up in patients with diffuse large B-cell lymphoma after first-line therapy

BackgroundThe purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose–positron emission tomography/computed tomography (FDG–PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy.Patients and methods: DLBCL patients receiving FDG–PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence.ResultsSeventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG–PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02–7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20–14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041).ConclusionsFDG–PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG–PET/CT during follow-up is indicated for patients <60 years with clinical signs of relapse and in patients >60 years with and without clinical signs of relapse.     

Will new drugs change the standard of care for patients with mantle cell lymphoma?

Mantle Cell lymphoma is a heterogeneous malignancy that has different subtypes with variable levels of aggressiveness. Research on the pathobiology of this disease is helping us understand the etiology for this heterogeneity and has the potential to guide future therapeutic options. The availability of the Ki67 proliferation index and the use of the MIPI score can help determine which of the numerous therapeutic options might be utilized. Minimal Residual Disease testing can act as a guide as to the potential benefit of maintenance therapy. This article discusses the current standard of care for Mantle Cell lymphoma and our current understanding of the pathobiology of the disease leading to strategies to improve patient outcomes with some of the newer targeted agents.     

An evaluation of the potential for drug–drug interactions between bendamustine and rituximab in indolent non-Hodgkin lymphoma and mantle cell lymphoma

Purpose

Bendamustine plus rituximab has been reported to be effective in treating lymphoid malignancies. This analysis investigated the potential for drug–drug interactions between the drugs in patients with indolent non-Hodgkin lymphoma or mantle cell lymphoma.

Methods

Data were derived from a bendamustine–rituximab combination therapy study, a bendamustine monotherapy study, and published literature on rituximab monotherapy and combination therapy. Analysis of the potential for rituximab to affect bendamustine systemic exposure included comparing bendamustine concentration–time profile following monotherapy to that following combination therapy and comparing model-predicted Bayesian bendamustine clearance in the presence and absence of rituximab. Analysis of the potential for bendamustine to affect rituximab systemic exposure included plotting observed minimum, median, and maximum serum rituximab concentrations at the end of rituximab infusion (EOI) and 24 h and 7 days post-infusion in patients receiving combination therapy versus concentrations reported in literature following rituximab monotherapy.

Results

The established population pharmacokinetic model following bendamustine monotherapy was evaluated to determine its applicability to combination therapy for the purpose of confirming lack of pharmacokinetic interaction. The model adequately described the bendamustine concentration–time profile following monotherapy and combination therapy in adults. There was no statistically significant difference in estimated bendamustine clearance either alone or in combination. Also, rituximab concentrations from EOI to 24 h and 7 days demonstrated a pattern of decline similar to that seen in rituximab studies without bendamustine, suggesting that bendamustine does not affect the rituximab clearance rate.

Conclusions

Neither bendamustine nor rituximab appears to affect systemic exposure of the other drug when coadministered.     

Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities – Long-term follow-up of a randomised trial

Introduction: Isolated limb perfusion (ILP) is a treatment option most commonly used in the treatment of melanoma in-transit metastases of the extremities. The principle idea is to surgically isolate a region of the body and then deliver a high concentration of a chemotherapeutic agent together with hyperthermia. There have been three randomised trials exploring whether adjuvant ILP to patients with recurrent or high-risk primary melanomas increases survival; one of these trials has now been updated with a 25-year follow-up.

Methods: The original study randomised 69 patients (between 1981 and 1989) with their first satellite or in-transit recurrence to either wide excision (WE group, n?=?36 patients) or to WE and adjuvant ILP (WE?+?ILP group, n?=?33 patients). Follow-up data 25 years later concerning survival and cause of death was retrieved from the Swedish National Cause of Death Register.

Results: In the WE?+?ILP group there were 20 deaths (61%) due to melanoma compared with 26 deaths (72%) in the WE group (p?=?0.31). Median melanoma-specific survival was 95 months for WE?+?ILP compared to 38 months for the WE group, an almost 5 year benefit without statistical significance (p?=?0.24).

Discussion: There is no evidence that adjuvant ILP prolongs survival in patients with high-risk or recurrent melanoma; however, the existing randomised trials are largely underpowered to detect such a difference. New studies are exploring systemic immunological effects of ILP, and a combination of regional therapy and immunotherapy may serve as a rationale for new trials using ILP in the future.     

Mastectomy without radiotherapy: outcome analysis after 10?years of follow-up in a single institution

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1-3, 4-9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.     

CT and MRI findings with histopathologic correlation of a unique bilateral orbital mantle cell lymphoma in Graves’ disease: a case report and brief review of literature

Bilateral orbital mantle cell lymphoma is rare. We present an unusual case report of a patient with Graves’ disease and no previous history of lymphoma, who was found to have bilateral orbital mantle cell lymphoma on CT and MR imaging which was confirmed histopathologically. To our knowledge, there have been no previously described cases of bilateral mantle cell lymphoma in Graves’ disease. Of particular radiologic interest, the left orbital mass presented in a bicompartmental fashion with a discreet intraconal component separated by a fat plane from an extraconal component that extended intraconally. In our review of radiologic literature, this presentation has not been described previously.     

Phase II trial and prediction of response of single agent tipifarnib in patients with relapsed/refractory mantle cell lymphoma: a Groupe d’Etude des Lymphomes de l’Adulte trial

Purpose

Farnesyltransferase (Ftase) was identified by gene-expression profiling and by preclinical evaluation in in vitro and in vivo mantle cell lymphoma (MCL) models as a rational therapeutic target in MCL, one of the most refractory B-cell lymphomas. We conducted a multicenter phase II study of a potent Ftase inhibitor, tipifarnib, in patients with relapsed or refractory MCL.

Methods

Tipifarnib was administered at 300 mg orally twice daily for the first 21 days of each 28-day cycle for 4 cycles, and in case of response for 6 cycles. Study endpoints were objective response at 4 and 6 cycles, progression free survival (PFS), overall survival, and toxicity. Prediction of response was retrospectively evaluated in the initial tumor biopsy by the RASGRP1/APTX gene expression ratio, and the AKAP13 expression level.

Results

Eleven patients (median age, 71 years) were enrolled. Patients received a median number of three prior therapies (range 1–11). Nine patients completed at least 3 cycles of tipifarnib. No grade III–IV hematological toxicities were recorded. One patient presented a complete response (CR) after 4 and a persistent CR at 6 cycles (ORR = 9%). Median PFS was 3 months (range 0.7–14.2). The RASGRP1/APTX gene expression ratio was higher in the responder (n = 1) while the AKAP13 expression was higher in the non-responders (n = 2). This corresponds to the expected result for predicting response to tipifarnib.

Conclusion

Treatment with tipifarnib relapsed or refractory MCL is associated with low response rates. Limited gene expression studies suggest that response may be associated with molecular targets.     

Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.     

Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib – Analysis of prognostic factors (EORTC-STBSG collaborative study)

Background

Long-term complete remissions remain a rare exception in patients with metastatic gastrointestinal stromal tumors (GIST) treated with IM (imatinib). To date the therapeutic relevance of surgical resection of metastatic disease remains unknown except for the use in palliative intent.

Patients and methods

We analyzed overall survival (OS) and progression-free survival (PFS) in consecutive patients with metastatic GIST who underwent metastasectomy and received IM therapy (n = 239).

Results

Complete resection (R0+R1) was achieved in 177 patients. Median OS was 8.7 y for R0/R1 and 5.3 y in pts with R2 resection (p = 0.0001). In the group who were in remission at time of resection median OS was not reached in the R0/R1 surgery and 5.1 y in the R2-surgery (p = 0.0001). Median time to relapse/progression after resection of residual disease was not reached in the R0/R1 and 1.9 years in the R2 group of patients, who were resected in response. No difference in mPFS was seen in patients progressing at time of surgery. Conclusions: Our analysis implicates possible long-term survival in patients in whom surgical complete remission can be achieved. Incomplete resection, including debulking surgery does not seem to prolong survival. Despite the retrospective character and likely selection bias, this analysis may help in decision making for surgical approaches in metastatic GIST.     

Hodgkin’s lymphoma in remission after first-line therapy: which patients need FDG–PET/CT for follow-up?

Background: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose–positron emission tomography (FDG–PET)/computed tomography (CT) during follow-up of patients with Hodgkin’s lymphoma.Patients and methods: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG–PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence.Results: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG–PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7–6.6] and symptoms (P < 0.0001, HR 4.9, 95% CI 2.4–9.9) as significant risk factors for relapse. By multivariate analysis, morphological residual mass was the only significant risk factor for early follow-up (<24 months) (P = 0.0019, HR 7.6, 95% CI 2.1–27.3). Advanced stage (P = 0.0426, HR 3.6, 95% CI 1.1–12.3) and the presence of symptoms (P = 0.0009, HR = 14.6, 95% CI 3.0–69.7) were found to be significant risk factors for later follow-up (>24 months).Conclusions: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG–PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG–PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG–PET/CT beyond 24 months.     

Evaluation of long-term outcome for patients with renal cell carcinoma after surgery: analysis of cancer deaths occurring more than 10 years after initial treatment

Objective

We evaluated the outcome of renal cell carcinoma (RCC) after surgery in a long-term follow-up study to elucidate the specific biological behaviors of RCC, such as late recurrence and late cancer-specific death.

Materials and methods

We retrospectively reviewed the clinical and pathological features of 625 patients who were diagnosed as having renal cell carcinoma at our institution from 1975 to 2006. We analyzed the parameters and outcomes for the patients who had received radical or partial nephrectomy. Pathological staging was reviewed again by two pathologists.

Results

The median age of the patients was 61 years (range 16–87). The median follow-up was 7.0 years (range 0.1–30.3). Of the 516 patients with localized or locally advanced RCC, 124 (24.0 %) had recurrence after surgery. Lung metastasis was observed most frequently. The 10-year cancer-specific survival rates were 92.4, 91.0, 64.1 and 11.8 % for stages I, II, III and IV, respectively. The late recurrence rates in patients with localized and locally advanced RCC 5 and 10 years after initial surgery were 8.5 and 3.7 %, respectively. Cancer death more than 10 years after initial treatment of the disease occurred in 16 patients. Of the 16 patients, 9 had localized disease at the time of the initial surgery. Specific findings that characterized them were not identified in these patients.

Conclusions

Late recurrence of RCC is not rare. Cancer-specific death more than 10 years after the initial treatment was observed in 16 patients with localized or advanced disease. No specific findings were identified to characterize these patients with late cancer death.     

Quality of life in older and frail patients after surgery for colorectal cancer—A follow-up study

ObjectiveThe incidence of colorectal cancer is increasing, mainly due to the aging of the population. Frailty, describing a state of increased vulnerability, is common in older patients, but frailty and high age are not necessarily contraindications to surgical treatment. However, limited data describing long-term outcomes after surgery in this patient group exist. In this clinical follow-up study, we aimed to examine long-term health-related quality of life in older surgical patients with colorectal cancer.Materials and MethodsPatients were recruited from a prospective multicenter study investigating frailty as a predictor of postoperative complications after surgery for colorectal cancer. A preoperative geriatric assessment was performed, and patients were classified as frail or non-frail. Patients responded to version 3.0 of The European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-C30 before surgery, 3 months postoperatively and at a long-term follow-up 16–28 months (median 22 months) after surgery. One-way repeated-measures analyses of variance were performed to examine changes in scores over time.Results180 patients with a mean age of 80 years were included at baseline, 138 at 3 months postoperatively, and 84 patients (69% of survivors) at long-term follow-up. A significant improvement in quality of life-scores was present 3 months after surgery, also in the subgroup of frail patients. At long-term follow-up, scores decreased, but to values above baseline.ConclusionHealth-related quality of life may be improved in older patients after surgery for colorectal cancer, even in patients who are classified as frail preoperatively.     

Lung carcinoma with spindle and/or giant cell： a clinicopathological analysis of 17 cases

Objective: Lung carcinoma with spindle and (or) giant cell (LCSG) is a rare epithelial malignant tumor. The aim of our study is to investigate the clinicopathological and prognostic characteristics of 17 cases of LCSGs. Methods: Among 421 patients underwent resection of lung carcinomas, 17 cases of LCSG were studied for clinical, gross and histological parameters. Follow-up information was obtained and analyzed to clarify prognostically significant parameters. Results: The LCSG patients consisted of 15 males and 2 females, with the age ranging from 45 to 78 years (median, 58 years); 5 cases of stage Ⅰ, 3 of stage Ⅱ, 9 of stage Ⅲ by pathological TNM staging; 2 cases of exclusively spindle cell carcinoma, 5 cases of lung carcinoma with spindle cell, 10 cases of lung carcinoma with giant-cell carcinoma. Cough, chest distress, or chest pain were the most common presenting symptoms, occurring in 15 patients (88.2%). Of 5 patients in stage Ⅰ, 4 were alive and free of relapse for more than 5 years. The difference in survival was statistically significant between LCSG and squamous cell carcinoma patients (median survival, 36 vs. 61 months; P = 0.027). Lymph node metastasis and carcinoma with giant cell were the hazardous factors impacting postoperative prognosis of LCSG patients. Conclusion: LCSG patients in early stage may have an optimistic outcome. Lung carcinomas with giant cell displayed multiple cell components in histopathology, and poor outcome due to more lymph node involved.     

Incidence and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer: Japan Clinical Oncology Group study—post hoc analysis of JCOG1009/1010

Gastric Cancer - A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for...