Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial.

PURPOSE: We prospectively evaluated the predictive value of therapy-induced reduction of tumor glucose use for subsequent response and patient survival in patients with gastric cancer treated by preoperative chemotherapy. PATIENTS AND METHODS: Forty-four consecutive patients with locally advanced gastric carcinomas were studied by positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of cisplatin-based polychemotherapy. On the basis of a previous study, a reduction of tumor FDG uptake by more than 35% was used as a criterion for a metabolic response. The metabolic response in FDG-PET was correlated with histopathologic response after completion of therapy (< 10% viable tumor cells in the resected specimen) and patient survival. RESULTS: Thirty-five (80%) of the 44 tumors were visualized with sufficient contrast for quantitative analysis (two of 19 intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In the 35 assessable patients, PET imaging after 14 days of therapy correctly predicted histopathologic response after 3 months of therapy in 10 (77%) of 13 responders and 19 (86%) of 22 nonresponders. Median overall survival for patients with a metabolic response has not been reached (2-year survival rate, 90%); for patients without a metabolic response, median survival was only 18.9 months (2-year survival rate, 25%; P =.002) CONCLUSION: This study prospectively demonstrates that in patients with gastric cancer, response to preoperative chemotherapy can be predicted by FDG-PET early during the course of therapy. By avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may markedly facilitate the use of preoperative chemotherapy.     

Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer.

PURPOSE: The aim of this study was to evaluate sequential F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) to predict patient outcome after the first and third cycle of neoadjuvant chemotherapy in advanced-stage (International Federation of Gynecology and Obstetrics stages IIIC and IV) ovarian cancer. PATIENTS AND METHODS: Thirty-three patients received three cycles of carboplatin-based chemotherapy, followed by cytoreductive surgery. Quantitative FDG-PET of the abdomen and pelvis was acquired before treatment and after the first and third cycle of chemotherapy. Changes in tumoral FDG uptake, expressed as standardized uptake values (SUV), were compared with clinical and histopathologic response; overall survival served as a reference. RESULTS: A significant correlation was observed between FDG-PET metabolic response after the first (P = .008) and third (P = .005) cycle of chemotherapy and overall survival. By using a threshold for decrease in SUV from baseline of 20% after the first cycle, median overall survival was 38.3 months in metabolic responders compared with 23.1 months in metabolic nonresponders. At a threshold of 55% decrease in SUV after the third cycle median overall survival was 38.9 months in metabolic responders compared with 19.7 months in nonresponders. There was no correlation between clinical response criteria (P = .7) or CA125 response criteria (P = .5) and overall survival. There was only a weak correlation (P = .09) between histopathologic response criteria and overall survival. CONCLUSION: Sequential FDG-PET predicted patient outcome as early as after the first cycle of neoadjuvant chemotherapy and was more accurate than clinical or histopathologic response criteria including changes in tumor marker CA125. FDG-PET appears to be a promising tool for early prediction of response to chemotherapy.     

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.     

Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer.

AIMS: This prospective study was designed to determine the utility of 18F-labelled deoxyglucose (FDG) in positron emission tomography (PET) (FDG-PET) for assessing the response to neoadjuvant chemoradiation therapy (CRT) in locally advanced oesophageal tumours. PATIENTS AND METHODS: Thirty-six patients with locally advanced oesophageal cancer (clinical T4 stage) without organ metastases, underwent FDG-PET before and 1 month after CRT. Patients were classified as major responders by serial FDG-PET when the post-CRT PET demonstrated a strong reduction of FDG uptake at the primary tumour site (>80% reduction of tumour-to-liver uptake ratio) without any abnormal FDG uptake elsewhere in the body. PET response was compared with histology obtained during post-induction transthoracic oesophagectomy. RESULTS: A strong correlation was found between the extent of lymph node (LN) involvement as shown by the pre-CRT PET and the major response rate (P = 0.001): such response occurred in nine of 11 N0M0 patients (82%), in three of nine N(1-2)M0 patients (33%) and in two of 16 patients (13%) with distant lymphatic spread. Such a correlation was not found for computed tomography or endoscopic ultrasonography. The sensitivity of serial FDG-PET for a major CRT response was 10 of 14 (71%), its specificity 18 of 22 (82%). The concordance between the response assessment by PET and histopathology was 78%. The median survival time after CRT of PET major responders compared with PET non-major responders was 16.3 months and 6.4 months, respectively. The metabolic response as measured by serial FDG-PET is a stronger prognostic factor for overall survival (P = 0.002) than the extent of LN involvement seen on the pretreatment FDG-PET (P = 0.087). CONCLUSIONS: These data indicate that CRT response as assessed by serial FDG-PET is strongly correlated with pathological response and survival.     

The new credo: induction chemotherapy in locally advanced gastric cancer: consequences for surgical strategies

Perioperative chemotherapy in stage II and stage III gastric cancer is now accepted as a standard of care in the Western world. Two randomized phase III studies have shown improved survival for patients with induction chemotherapy followed by surgery compared with surgery alone. It is generally accepted that patients who respond to induction therapy have a significantly improved survival compared with that in nonresponding patients. Unfortunately no prospectively tested markers predicting response and/or prognosis are available for clinical practice. In adenocarcinomas of the esophagogastric junction (AEG), fluorodeoxyglucose-positron emission tomography (FDG-PET) prospectively was established as a surrogate predicting response and prognosis. The MUNICON (Metabolic response evalUatioN for Individualisation of neoadjuvant Chemotherapy in oesOphageal and oesophagogastric adeNocarcinoma) I study confirmed prospectively the usefulness of early metabolic response evaluation and showed the feasibility of a PET-guided treatment algorithm. These findings are an important step forward in the tailoring of multimodal treatment in accordance with tumor biology. In gastric cancer, we have analyzed FDG-PET in a prospective study. In gastric cancer the issue is more complicated, because about 30% of gastric cancers cannot be visualized with sufficient contrast for quantification. Insufficient FDG uptake is mostly associated with diffuse-type gastric cancer with signet ring cells and mucinous content. In FDG-avid patients, FDG-PET can be used for response evaluation, comparable to that in AEG. The prognosis of FDG-nonavid patients is similar to that in metabolic nonresponders. The addition of new tracers such as fluorothymidine may increase the sensitivity of PET in the future. Treatment concepts such as immediate resection after only 2 weeks of induction therapy with or without adjuvant treatment could be considered in metabolic nonresponders, or modified chemotherapy regimens, possibly including biologically targeted drugs, could be considered in those with FDG-nonavid tumors. Presented in part at the 7th International Gastric Cancer Congress, Sao Paulo, Brazil, 2007     

Reduction of glucose metabolic activity is more accurate than change in size at predicting histopathologic response to neoadjuvant therapy in high-grade soft-tissue sarcomas

PURPOSE: Change in tumor size as classified by Response Evaluation Criteria in Solid Tumors poorly correlates with histopathologic response to neoadjuvant therapy in patients with soft-tissue sarcomas. The aim of this study was to prospectively evaluate whether positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) allows for a more accurate evaluation of histopathologic response. EXPERIMENTAL DESIGN: From January 2005 to January 2007, 42 patients with resectable biopsy-proven high-grade soft-tissue sarcoma underwent a FDG-PET/computed tomography scan before and after neoadjuvant treatment. Relative changes in tumor FDG uptake and size from the baseline to the follow-up scan were calculated, and their accuracy for assessment of histopathologic response was compared by receiver operating characteristic curve analysis. Histopathologic response was defined as > or =95% tumor necrosis. RESULTS: In histopathologic responders (n = 8; 19%), reduction in tumor FDG uptake was significantly greater than in nonresponders (P < 0.001), whereas no significant differences were found for tumor size (P = 0.24). The area under the receiver operating characteristic curve for metabolic changes was 0.93, but only 0.60 for size changes (P = 0.004). Using a 60% decrease in tumor FDG uptake as a threshold resulted in a sensitivity of 100% and a specificity of 71% for assessment of histopathologic response, whereas Response Evaluation Criteria in Solid Tumors showed a sensitivity of 25% and a specificity of 100%. CONCLUSION: Quantitative FDG-PET was significantly more accurate than size-based criteria at assessing histopathologic response to neoadjuvant therapy. FDG-PET should be considered as a modality to monitor treatment response in patients with high-grade soft-tissue sarcoma.     

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.

PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.     

Metabolic characterization of childhood brain tumors: comparison of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography

BACKGROUND: Positron emission tomography (PET) scans of primary brain tumors were performed in pediatric patients to examine whether metabolic characteristics could be used as an index of clinical aggressiveness. METHODS: Twenty-seven pediatric patients with untreated primary central nervous system neoplasms were studied with PET scans using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) and/or L-[methyl-(11)C] methionine (MET). Metabolic characteristics as assessed with FDG and MET standardized uptake values (SUV) and SUV-to-normal brain ratios were compared with histopathology and selected histochemical features such as proliferation activity (Ki-67(MIB-1)) and apoptotic, vascular, and cell density indices. The median followup time was 43 months. RESULTS: The accumulation of both FDG and MET was significantly higher in high-grade than in low-grade tumors, but a considerable overlap was found. The accumulation of both tracers was associated positively with age. High-grade tumors showed higher proliferative activity and vascularity than the low-grade tumors. In univariate analysis, FDG-PET, MET-PET, and apoptotic index were independent predictors of event-free survival. CONCLUSION: We found that both FDG and MET uptake in pediatric brain tumors are associated with malignancy grade. However, no clear limits of SUVs and SUV-to-normal brain ratios can be set between low-grade and high-grade tumors, which makes the assessment of malignancy grade using metabolic imaging with PET scan difficult in individual cases. Although FDG-PET and MET-PET do not compensate for histopathologic evaluation, they may give valuable additional information especially if invasive procedures to obtain histopathologic samples are not feasible.     

Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer.

PURPOSE: To address the role of positron emission tomography (PET) using [(18)F]fluorodeoxyglucose (FDG) to monitor primary (neoadjuvant) chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Quantification of regional FDG uptake of the breast acquired after the first and second courses of chemotherapy was compared with the baseline scan in 22 patients with a total of 24 breast carcinomas. To evaluate the predictive value of PET imaging, histopathologic response after completion of chemotherapy classified as gross residual disease (GRD) or minimal residual disease (MRD) served as the gold standard. RESULTS: Significant differences in tracer uptake between nonresponding tumors (GRD) and responding lesions (MRD) were observed (P <.05) as early as after the first course of chemotherapy. Tracer uptake showed little change in tumors with GRD found later in pathologic analysis but decreased sharply to the background level in most tumors with MRD. After the first course, all responders were correctly identified (sensitivity 100%, specificity 85%) by a standardized uptake value decrease below 55% of the baseline scan. At this threshold, histopathologic response could be predicted with an accuracy of 88% and 91% after the first and second courses of therapy, respectively. CONCLUSION: This study demonstrates that in patients with advanced breast cancer undergoing primary chemotherapy, FDG-PET differentiates responders from nonresponders early in the course of therapy. This may help improve patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose-intensive preoperative chemotherapy in responding patients.     

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET

Purpose: To evaluate the use of positron emission tomography using ¹⁸F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. Material and methods: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with ≤2?cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n?=?26) and 2 weeks after initiation of therapy (n?=?17). FDG uptake was quantitatively assessed by standardized uptake values. Results: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median ?44% (?75 to 2); in non-responders, it decreased by a median of ?15% (?46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. Conclusion: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.     

Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use.

PURPOSE: To prospectively evaluate the use of positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) to predict response to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC scheduled to undergo platinum-based chemotherapy were eligible for this study. Patients were studied by FDG-PET before and after the first cycle of therapy. Based on previous studies, a reduction of tumor FDG uptake by more than 20% as assessed by standardized uptake values (SUV) was used as a criterion for a metabolic response. Furthermore, changes in tumor SUVs were compared with changes in FDG net-influx constants (Ki) and tumor/muscle ratios (t/m). RESULTS: Fifty-seven patients were included in the study. There was a close correlation between metabolic response and best response to therapy according to Response Evaluation Criteria in Solid Tumors (P <.0001; sensitivity and specificity for prediction of best response, 95% and 74%, respectively). Median time to progression and overall survival were significantly longer for metabolic responders than for metabolic nonresponders (163 v 54 days and 252 days v 151 days, respectively). Similar results were obtained when Ki was used to assess tumor glucose use, whereas changes in t/m showed considerable overlap between responding and nonresponding tumors. CONCLUSION: In NSCLC, reduction of metabolic activity after one cycle of chemotherapy is closely correlated with final outcome of therapy. Using metabolic response as an end point may shorten the duration of phase II studies evaluating new cytotoxic drugs and may decrease the morbidity and costs of therapy in nonresponding patients.     

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.     

Tumor response and survival predicted by post-therapy FDG-PET/CT in anal cancer

PURPOSE: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. PATIENTS AND METHODS: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. RESULTS: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). CONCLUSIONS: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.     

PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial

BACKGROUND: In patients with locally advanced adenocarcinoma of the oesophagogastric junction (AEG), early metabolic response defined by 18-fluorodeoxyglucose-PET ([(18)F]FDG-PET) during neoadjuvant chemotherapy is predictive of histopathological response and survival. We aimed to assess the feasibility of a PET-response-guided treatment algorithm and its potential effect on prognosis. METHODS: Between May 27, 2002, and Aug 4, 2005, 119 patients with locally advanced adenocarcinoma of AEG type 1 (distal oesophageal adenocarcinoma) or type 2 (gastric cardia adenocarcinoma) were recruited into this prospective, single-centre study. All patients were assigned to 2 weeks of platinum and fluorouracil-based induction chemotherapy (evaluation period). Those with decreases in tumour glucose standard uptake values (SUVs), predefined as decreases of 35% or more at the end of the evaluation period and measured by PET, were defined as metabolic responders. Responders continued to receive neoadjuvant chemotherapy of folinic acid and fluorouracil plus cisplatin, or folinic acid and fluorouracil plus cisplatin and paclitaxel, or folinic acid and fluorouracil plus oxaliplatin for 12 weeks and then proceeded to surgery. Metabolic non-responders discontinued chemotherapy after the 2-week evaluation period and proceeded to surgery. The primary endpoint was median overall survival of metabolic responders and non-responders. Secondary endpoints were median event-free survival, postoperative complications and mortality, number of residual tumour-free (R0) resections, and histopathological responses. This study has been registered in the European Clinical Trials Database (EudraCT) as trial 2007-003356-11. FINDINGS: 110 patients were evaluable for metabolic responses. 54 of these patients had metabolic responses (ie, decrease of 35% or more in tumour glucose SUV) after 2 weeks of induction chemotherapy, corresponding to a response of 49% (95% CI 39-59). 104 patients had tumour resection (50 in the responder group and 54 in the non-responder group). After a median follow-up of 2.3 years (IQR 1.7-3.0), median overall survival was not reached in metabolic responders, whereas median overall survival was 25.8 months (19.4-32.2) in non-responders (HR 2.13 [1.14-3.99, p=0.015). Median event-free survival was 29.7 months (95% CI 23.6-35.7) in metabolic responders and 14.1 months (7.5-20.6) in non-responders (hazard ratio [HR] 2.18 [1.32-3.62], p=0.002). Major histological remissions (<10% residual tumour) were noted in 29 of 50 metabolic responders (58% [95% CI 48-67]), but no histological response was noted in metabolic non-responders. INTERPRETATION: This study confirmed prospectively the usefulness of early metabolic response evaluation, and shows the feasibility of a PET-guided treatment algorithm. These findings might enable tailoring of multimodal treatment in accordance with individual tumour biology in future randomised trials.     

The predictive value of 18F-FDG-PET early evaluation in patients with metastatic gastric adenocarcinoma treated with chemotherapy plus cetuximab

BACKGROUND: The aim of the study was to evaluate whether the therapy-induced reduction of the (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) maximum standardized uptake value in patients with advanced gastric adenocarcinoma treated with chemotherapy plus cetuximab could predict the objective response and outcome early during the treatment. METHODS: The study was performed as a part of a phase II trial evaluating cetuximab plus the leucovorin/5-fluorouracil/irinotecan (FOLFIRI) regimen. The objective response was evaluated according to the response evaluation criteria in solid tumors (RECIST) every 6 weeks. The early metabolic response evaluated by 18F-FDG-PET was assessed according to our own evaluated cutoff value (<35%) after receiver operating characteristic (ROC) analysis. RESULTS: Twenty of 22 patients had positive baseline 18F-FDG-PET. The best RECIST response was: complete response (CR), 3; partial response (PR), 9; stable disease (SD), 8. Twelve patients (60%) were classified as metabolic responders and 8 (40%) as nonresponders. At the median follow-up time of 11 months, median time to disease progression (TTP) and overall survival (OS) for early metabolic responders versus nonresponders were 11 versus 5 months (P = 0.0016) and 16 versus 6 months (P = 0.1493), respectively. CONCLUSION: The early metabolic response evaluated by 18F-FDG-PET predicted the clinical outcome in this series of patients with advanced gastric cancer treated with chemotherapy plus cetuximab.     

The Diagnostic Value of FDG-PET/CT for Urachal Cancer

Background: Urachal carcinoma (UrC) is a rare malignancy that often presents at an advanced stage with metastases in up to a quarter of patients. There is no consensus on the optimal form of staging for patients with UrC. In the present study, we evaluated the diagnostic value of ¹⁸F-fluorodeoxyglucose–positron emitted tomography/computed tomography (FDG-PET/CT) for UrC.Patients and Methods: We evaluated 40 consecutive patients who were staged for urachal cancer between 2010 and 2020. They underwent a total of 62 FDG-PET/CTs (40 for primary staging, and 22 during follow-up), which were compared with standard-of-care contrast-enhanced CT (CECT). The metabolic detection of primary tumors, lymph node metastases (LNMs), peritoneal metastases (PMs), distant metastases (DMs), and local recurrence by FDG-PET/CT was evaluated. Sensitivity and specificity were calculated compared with CECT. Histopathology or follow-up imaging was the reference standard.Results: Of all 40 patients, 33 patients (83%) had urachal adenocarcinoma—26 (65%) with a mucinous component and 7 (17%) with invasive urothelial carcinoma. All local UrC tumors could be visualized on CT, and 80% showed increased FDG uptake. At initial staging, FDG-PET/CT detected FDG-avid LNMs, PMs, and DMs in 50%, 17%, and 25% of patients, respectively. These metastases were also visualized on CECT. During follow up, FDG-PET/CT revealed FDG-avid local recurrences that were not seen on CT in two out of eight patients (25%).Conclusion: The present study demonstrates that most UrC can be visualized on FDG-PET/CT. At initial diagnosis, FDG-PET/CT does not seem to yield additional information compared with CECT; however, FDG-PET/CT may be helpful during follow-up. This is a small study, and the findings should be corroborated with larger series.     

Metabolic flare: indicator of hormone responsiveness in advanced breast cancer.

PURPOSE: The purpose of this study was to investigate whether positron emission tomography (PET) with the glucose analog [(18)F]fluorodeoxyglucose (FDG) and the estrogen analog 16 alpha-[(18)F]fluoroestradiol-17 beta (FES), performed before and after treatment with tamoxifen, could be used to detect hormone-induced changes in tumor metabolism (metabolic flare) and changes in available levels of estrogen receptor (ER). In addition, we investigated whether these PET findings would predict hormonally responsive breast cancer. PATIENTS AND METHODS: Forty women with biopsy-proved advanced ER-positive (ER(+)) breast cancer underwent PET with FDG and FES before and 7 to 10 days after initiation of tamoxifen therapy; 70 lesions were evaluated. Tumor FDG and FES uptake were assessed semiquantitatively by the standardized uptake value (SUV) method. The PET results were correlated with response to hormonal therapy. RESULTS: In the responders, the tumor FDG uptake increased after tamoxifen by 28.4% +/- 23.3% (mean +/- SD); only five of these patients had evidence of a clinical flare reaction. In nonresponders, there was no significant change in tumor FDG uptake from baseline (mean change, 10.1% +/- 16.2%; P =.0002 v responders). Lesions of responders had higher baseline FES uptake (SUV, 4.3 +/- 2.4) than those of nonresponders (SUV, 1.8 +/- 1.3; P =.0007). All patients had evidence of blockade of the tumor ERs 7 to 10 days after initiation of tamoxifen therapy; however, the degree of ER blockade was greater in the responders (mean percentage decrease, 54.8% +/- 14.2%) than in the nonresponders (mean percentage decrease, 19.4% +/- 17.3%; P =.0003). CONCLUSION: The functional status of tumor ERs can be characterized in vivo by PET with FDG and FES. The results of PET are predictive of responsiveness to tamoxifen therapy in patients with advanced ER(+) breast cancer.     

Prognostic significance of metabolic response by positron emission tomography after neoadjuvant chemotherapy for resectable malignant pleural mesothelioma

BackgroundTo select optimal candidates for extrapleural pneumonectomy (EPP), we retrospectively evaluated the usefulness of metabolic response by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemotherapy to predict prognosis for patients with resectable malignant pleural mesothelioma (MPM) who underwent EPP in a multicenter study.Patients and methodsWe carried out high-resolution CT (HRCT) and FDG-PET/CT before and after neoadjuvant platinum-based chemotherapy on 50 patients with clinical T1–3 N0-2 M0 MPM who underwent EPP ± postoperative hemithoracic radiotherapy. A decrease of ≥30% in the tumor maximum standardized uptake value (SUV_max) was defined as a metabolic responder. The radiologic response using the modified RECIST or metabolic response and surgical results were analyzed.ResultsThe median overall survival (OS) from diagnosis was 20.5 months. Metabolic responders significantly correlated to OS with median OS for metabolic responders not reached versus 18.7 months for non-responders. No correlation was observed between OS and radiologic response with median OS for radiologic responders and non-responders. Based on the multivariate Cox analyses, decreased SUV_max and epithelioid subtype were significantly independent factors for OS.ConclusionsThe metabolic response after neoadjuvant chemotherapy is an independent prognostic factor for patients with resectable MPM. Patients with metabolic responder or epithelioid subtype may be good candidates for EPP.     

Importance of primary site in assessing chemotherapy response and 7-year survival data in advanced squamous-cell carcinomas of the head and neck treated with initial combination chemotherapy without cisplatin

Two hundred eight patients with advanced head and neck squamous-cell carcinomas were treated between 1975 and 1982 with schedule A chemotherapy containing vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours followed by a folinic acid rescue. Chemotherapy was administered as initial treatment on days 1 and 14 before "curative" local therapy. Toxicity was minimal and patient compliance was 100%. Chemotherapy response was assessed on day 28 in 200 patients: 132 (66%) had an objective response and 68 (34%) were judged to be nonresponders. The complete remission (CR) rate following local therapy was significantly greater in chemotherapy responders (78%) than nonresponders (49%) (P less than .001). Overall median survival figures were 32 months for all patients, 37 months for all chemotherapy responders, and 69 months for all patients achieving CR. Analysis by tumor site showed that oral cavity or nasopharyngeal tumors responded well to initial chemotherapy (P less than .05 and P less than .01) compared with all other sites. This high response rate was not necessarily associated with increased survival, since the median survival of chemotherapy responders for oral cavity lesions was only 22 months, although in nasopharyngeal tumors, median survival figures were 64 months. Furthermore, the longest median survival duration of 69 months was observed in patients with laryngeal tumors, although these had a lower response rate (61%) to initial chemotherapy. Therefore, response to initial chemotherapy is not automatically a favorable prognostic sign. Survival figures appear markedly influenced by tumor site.     

Evaluation of responses to chemoembolization in patients with unresectable hepatocellular carcinoma

BACKGROUND: The authors used computed tomography (CT) scans to correlate the changes in tumor vascularity, necrosis, and size with response and survival after transcatheter arterial chemoembolization (TACE) in patients with advanced, unresectable, hepatocellular carcinoma (HCC). METHODS: The authors studied 72 patients with biopsy-proven, unresectable HCC and focused on 186 individual tumor masses. A baseline, multiphase, helical CT was performed and at least three follow-up CT scans were performed after treatment by TACE. Tumors were classified as hypervascular or hypovascular and patients were classified as responders or nonresponders based on CT evidence of altered tumor size, tumor necrosis, and the appearance of new tumors. A new scoring system was used to monitor patient response to TACE. RESULTS: Thirty-eight patients were responders and 34 were nonresponders. Patient survival was significantly increased (P = 0.009) in patients who were hypervascular responders. Survival also was increased in hypervascular nonresponders compared with hypovascular nonresponders (P = 0.008) and in hypovascular responders compared with hypovascular nonresponders (P = 0.002). Response to chemoembolization was found to be significantly (P = 0.02) and inversely proportional to tumor size, but the number of tumor foci in an individual patient was not predictive. CONCLUSIONS: TACE appears to result in improved survival among HCC patients with hypervascular tumors who responded to therapy. However, even patients classified by CT as hypervascular nonresponders and hypovascular responders have improved survival.