Vinorelbine plus cisplatin versus cisplatin plus vindesine and mitomycin C in stage IIIB-IV non-small cell lung carcinoma: a prospective randomized study

This study was performed to investigate the utility of FDG-PET for: (1) initial staging, and (2) restaging of the primary and mediastinal nodal lesions 2 weeks after the completion of preoperative chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Twenty-six patients with histologically confirmed stage III NSCLC were accrued to this study from April 1993 to July 1998. They included 21 with stage IIIA (N2) NSCLC who were enrolled into an institutional phase II study, and 5 patients with a highly selected subset of stage IIIB disease characterized by the presence of microscopic metastatic disease in contralateral mediastinal lymph nodes who were also treated with preoperative chemoradiotherapy; N3 lesions (n=3) and minimal T4 lesions. Demographic characteristics included median age 62 years (a range from 47 to 73) and gender ratio of male 15 to female 11. Histologic types of tumor consisted of squamous cell carcinoma 6, adenocarcinoma 11, large cell carcinoma 5, and non-small cell carcinoma 4. All patients had FDG-PET imaging of the chest before the initiation and 2 weeks after completion of preoperative therapy. The FDG-PET images were evaluated qualitatively for uptake at the primary tumor sites and mediastinal lymph nodes. Standard uptake values (SUVs) were also calculated for the primary tumors and all PET findings were correlated with surgical histopathologic data. Preoperative chemoradiotherapy resulted in complete pathologic response in 8 of 26 primary lesions. By qualitative analysis, 96% of these tumors showed level 3 or 4 uptake before preoperative chemoradiotherapy. After chemoradiotherapy, 57% (15/26) of patients showed at least a one level decrease in uptake, and the sensitivity and specificity of FDG-PET for differentiating residual tumor from pathologic complete response were 67% (12/18) and 63% (5/8). Mean SUV was 14.87+/-7.11 at baseline and decreased to 5.72+/-3.35 after chemoradiotherapy (n=21, P<0.00001). When a value of 3.0 was used as the SUV cut-off, sensitivity and specificity were 88 and 67%, respectively. The mean values of visual intensity were 3.87+/-0.35 and 3.8+/-0.51 for patients who achieved pathologic complete response (n=8) and for those who showed residual cancer after the preoperative therapy (n=18), respectively. The mean SUVs were 16.97+/-8.52 and 14.03+/-6.61 for patients who achieved pathologic complete response (n=6) and for those who showed residual cancer (n=15) after the preoperative therapy, respectively. Therefore, the degree of FDG uptake before preoperative chemoradiotherapy did not provide predictive value for subsequent tumor response. For mediastinal initial staging, the sensitivity and specificity of FDG-PET were 75 and 90.5%. The sensitivity and specificity of FDG-PET for mediastinal restaging were 58.0 and 93.0%. These results indicate that FDG-PET is useful for monitoring the therapeutic effect of neoadjuvant chemoradiotherapy in patients with stage III NSCLC. For the primary lesions, SUV based analysis has high sensitivity but limited specificity for detecting residual tumor. In contrast, for restaging of mediastinal lymph nodes, FDG-PET is highly specific, but has limited sensitivity.     

2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma

BACKGROUND: The current study was performed to assess the value of 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting the pathologic response and survival of patients with esophageal carcinoma treated with preoperative chemoradiation (CRT) and tumor resection. Preliminary reports suggest that FDG-PET may be predictive of the response of esophageal carcinoma patients to preoperative CRT. METHODS: Eighty-three patients with resectable esophageal carcinoma who underwent preoperative CRT and FDG-PET and tumor resection were evaluated for pathologic response to CRT, percent residual tumor, and survival. RESULTS: The majority of patients in the current study were men (74 of 83 patients; 89%). Most tumors were adenocarcinomas (73 of 83 tumors; 88%) and clinical (EUS)T3/4 (69 tumors; 83%) or N1 (46 tumors; 55%). FDG-PET after preoperative CRT identified pathologic responders but failed to rule out microscopic residual tumor in 13 of 73 cases (18%). Pathologic response was found to correlate with the post-CRT FDG-PET standardized uptake value (SUV) (P = 0.03) and a post-CRT FDG-PET SUV of or 4 was found to be the only preoperative factor to correlate with decreased survival (2-year survival rate of 33% vs. 60%; P = 0.01). On univariate Cox regression analysis, only post-CRT FDG-PET was found to be correlated with post-CRT survival (P = 0.04). CONCLUSIONS: Post-CRT FDG-PET was found to be predictive of pathologic response and survival in patients with esophageal carcinoma who undergo preoperative CRT. Esophagectomy should still be considered even if the post-CRT FDG-PET scan is normal because microscopic residual disease cannot be ruled out.     

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.     

Correlation of molecular response as measured by 18-FDG positron emission tomography with outcome after chemoradiotherapy in patients with esophageal carcinoma

PURPOSE: To determine whether 18-fluorodeoxyglucose positron emission tomography (PET) computed tomography scans predict the pathologic complete response and disease-free and overall survival in patients with esophageal carcinoma undergoing definitive or preoperative chemoradiotherapy. METHODS AND MATERIALS: The records of patients with esophageal carcinoma presenting for definitive or preoperative treatment and undergoing pre- and post-treatment 18-fluorodeoxyglucose PET-computed tomography scans were retrospectively reviewed. The histologic type, T stage, and nodal status were the variables investigated to determine a relationship with the baseline standardized uptake value (SUV) of the primary tumor at diagnosis. We also attempted to determine whether a relationship exists between the percent decrease in SUV and a pathologic complete response, overall and disease-free survival. RESULTS: A total of 81 patients, 14 women and 67 men, underwent 18-fluorodeoxyglucose PET-computed tomography scanning before treatment and 63 also had post-treatment scans. T stage and tumor location predicted in univariate, but not multivariate, analysis for the initial SUV. Of the patients with a postchemoradiotherapy SUV of <2.5, 66% had tumor in the surgical specimen and 64% of patients had positive lymph nodes at surgery that were not imaged on the postchemoradiotherapy PET scan. A trend existed for post-treatment SUV and the days from radiotherapy to surgery to predict for a pathologic complete response (p = 0.09 and p = 0.08, respectively). The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group (p = 0.01). CONCLUSIONS: A correlation was found between the depth of tumor invasion and the baseline SUV. The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group. Caution should be exercised in using post-treatment PET scans to determine the necessity for surgical resection.     

False-positive findings on [18F]FDG-PET caused by non-neoplastic cellular elements after neoadjuvant chemoradiotherapy for non-small cell lung cancer

We report two patients with non-small cell lung cancer who had a pathologically complete response after neoadjuvant chemoradiotherapy, although they had positive [(18)F]fluoro-deoxyglucose positron emission tomography ([(18)F]FDG-PET) scans. They underwent concurrent chemoradiotherapy, which resulted in a partial response determined by computed tomography (CT). While [(18)F]FDG-PET after chemoradiotherapy was positive, pathological examination showed that the tumors were fibrotic lesions with infiltration of lymphocytes and macrophages, with the appearance of metaplastic epithelial cells. The reasons for the false-positive results on [(18)F]FDG-PET were considered to be the high uptake of FDG in non-neoplastic inflammatory cellular elements, i.e. macrophages, lymphocytes and metaplastic epithelial cells, and squamous metaplasia induced by chemoradiotherapy. Although several studies demonstrated that [(18)F]FDG-PET could predict the response of neoadjuvant treatment of non-small cell lung cancer, one should bear in mind that false-positive results could be observed in pathological complete response of non-small cell lung cancer after neoadjuvant chemoradiotherapy.     

Clinical implications of initial FDG-PET/CT in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

Purpose

The present study evaluated the predictive and prognostic impact of initial fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with locally advanced rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT).

Methods

Eighty-one consecutive patients with locally advanced rectal cancer (cT3-T4 N?/N+) treated with neoadjuvant CCRT were enrolled. The FDG-PET/CT parameters, including the SUVmax, metabolic tumor volume (MTV, 50 % of SUVmax), and multiplication of the SUVmean and MTV (total lesion glycolysis, TLG), were analyzed in relation to the pathologic response and disease recurrence.

Results

Five patients (6.2 %) achieved a pathologic complete response (pCR) after CCRT followed by surgery. None of the FDG-PET/CT parameters was identified as a predictive factor for pCR. After a median follow-up period of 26.7 (range 10.9–63.3) months, 19 patients (23.5 %) presented a local and/or distant recurrence. In a multivariate analysis including the clinicopathologic parameters, the TLG of the primary tumor was associated with a worse disease-free survival after neoadjuvant CCRT (HR 20.035, 95 % CI 1.726–232.559; P = 00.017).

Conclusions

The TLG of the primary tumor in the initial FDG-PET/CT can be considered as a prognostic factor for patients with locally advanced rectal cancer treated with neoadjuvant CCRT.     

Prognostic and predictive value of baseline and posttreatment molecular marker expression in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

PURPOSE: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. METHODS AND MATERIALS: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. RESULTS: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. CONCLUSIONS: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.     

Early evaluation of the response to radiotherapy of patients with squamous cell carcinoma of the head and neck using 18FDG-PET

The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1 month after completion of RT was not too rapid for evaluating the response to radiation.     

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.     

Posttreatment FDG-PET uptake in the supraglottic and glottic larynx correlates with decreased quality of life after chemoradiotherapy

PURPOSE: Inflammation and increased metabolic activity associated with oxidative stress in irradiated normal tissues may contribute to both complications following radiotherapy and increased glucose uptake as detected by posttherapy fluorodeoxyglucose (FDG)-PET imaging. We sought to determine whether increased glucose uptake in normal tissues after chemoradiotherapy is associated with increased toxicity. METHODS AND MATERIALS: Consecutive patients with locoregionally advanced head and neck cancers treated with intensity-modulated radiation therapy and free of recurrence at 1 year were studied. FDG-PET imaging was obtained at 3 and 12 months posttreatment. Standardized uptake value (SUV) levels were determined at various head and neck regions. Functional outcome was measured using a quality of life questionnaire and weight loss and type of diet tolerated 1 year after therapy. A one-tailed Pearson correlation test was used to examine associations between SUV levels and functional outcome measures. RESULTS: Standardized uptake value levels in the supraglottic and glottic larynx from FDG-PET imaging obtained 12 months posttreatment were inversely associated with quality of life measures and were correlated with a more restricted diet 1 year after therapy. SUV levels at 3 months after therapy did not correlate with functional outcome. Increases in SUV levels in normal tissues between 3 and 12 months were commonly found in the absence of recurrence. CONCLUSION: Altered metabolism in irradiated tissues persists 1 year after therapy. FDG-PET scans may be used to assess normal tissue damage following chemoradiotherapy. These data support investigating hypermetabolic conditions associated with either inflammation, oxidative stress, or both, as causal agents for radiation-induced normal tissue damage.     

The predictive value of clinical evaluation of response to neoadjuvant chemoradiation therapy for rectal cancer

INTRODUCTION: Multimodality therapy has become the standard treatment for patients with locally advanced (T3 and T4) rectal carcinoma. Accurate preoperative staging of the patients with rectal cancer has increased in importance because the selection of patients with transmural rectal cancer (T3 or T4) or node-positive disease leads to a previous nonsurgical neoadjuvant treatment. The purpose of this study was to evaluate the predictive value of the clinical response to neoadjuvant therapy on the basis of pathological results obtained on rectal cancer patients treated by chemoradiotherapy and surgery. METHODS: From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were studied at our department and enrolled in a neoadjuvant protocol of chemoradiotherapy followed by surgery. All patients were treated by 30 days of chemoradiotherapy. At the end of the chemoradiotherapy, each patient underwent clinical examination, including digital rectal examination, proctoscopy and abdominal-pelvic computerized tomography to define the clinical response to the chemoradiotherapy. Surgical resection was performed in all patients three weeks after the end of chemoradiotherapy, and histological analysis was performed on all resected specimens. RESULTS: The clinical complete response rate corresponded to the pathological complete response rate, whereas the clinical evaluation overestimated partial response and stable disease. The pathologic examination revealed that 3.5% of clinical partial responses and 3.4% of clinical stable disease were really pathological progressive disease. Clinical partial response and clinical stable disease positive predictive values were 92.8% and 90.9%, respectively, whereas the clinical progressive disease negative predictive value was 20%. Then, 6.9% of patients believed to have responded to the therapy, or not to have responded or worsened, actually had worsened by the end of the chemoradiotherapy. CONCLUSIONS: Positive and negative predictive values, in particular for partial response and stable disease, of clinical evaluation of the response to chemoradiotherapy were not high enough to consider clinical evaluation accurate enough to make treatment decisions.     

18FDG-PET评价局部晚期和晚期非小细胞肺癌化疗的客观疗效

 目的 前瞻性地探索18-氟脱氧葡萄糖-正电子发射计算机断层扫描（18FDG-PET）的SUV值标准与实体瘤疗效评价标准（RECIST）标准评价非小细胞肺癌（NSCLC）化疗的客观疗效是否具有一致性。方法 初治不可切除的局部晚期和晚期NSCLC患者前瞻性入组，行两周期含铂双药方案全身化疗。按RECIST标准和SUV值标准（2个周期化疗后SUV值下降大于30 %）互为盲法分别评价肿瘤客观疗效。用配对计数资料的χ2检验和κ系数检验比较18FDG-PET代谢缓解与RECIST标准的客观疗效是否具有一致性（SPSS13.0）。结果 不可切除的局部晚期8例，晚期35例。18FDG-PET代谢缓解与按RECIST标准评价的疗效具有明显的一致性（P＜0.001）。18FDG-PET评价NSCLC化疗客观疗效的敏感性、特异性、准确性、阳性预测值和阴性预测值分别是94 %、70 %、80 %、67 %和95 %。结论 18FDG-PET可以评价局部晚期和晚期NSCLC化疗的客观疗效。     

Can FDG-PET/CT predict early response to neoadjuvant chemotherapy in breast cancer?

Purpose

Neoadjuvant chemotherapy (NAC) in breast cancer is currently used not only for locally advanced tumors, but also for large operable tumors when breast preservation is considered. It also provides the opportunity to evaluate chemotherapy tumor response. Our aim was to correlate the relative change in the standardized uptake value (SUV) of ¹⁸F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET/CT) with pathologic response after NAC.

Methods

We prospectively evaluated 40 patients with invasive ductal breast carcinomas from February 2010 to December 2011. FDG-PET/CT was performed at baseline and after the second cycle of NAC. All patients underwent surgery after NAC. Pathologic response was evaluated according to Residual Cancer Burden (RCB) index.

Results

The mean age was 41.9 years. Median primary tumor size was 6 cm. Pathologic complete response (pCR) was obtained in 12 (30%) patients. The tumor baseline mean maximum SUV (SUVmax), and after second cycle were: 8.97 (sd.4.3) and 4.07 (sd.3.2), respectively. The relative change (ΔSUV) after the second course of NAC was significantly higher for patients with pCR (−81.58%) when compared to the non-pCR patients (−40.18%) (p = 0.001). The optimal ΔSUV threshold that discriminates between pCR and non-pCR was −71.8% (83.3% sensitivity; 78.5% specificity). Moreover, the optimal ΔSUV threshold to discriminate between NAC responders and non-responders was −59.1% (68% sensitivity; 75.0% specificity).

Conclusions

Our data suggest that the FDG-PET/CT ΔSUV after the second course of NAC can predict pathological response in ductal breast carcinomas, and potentially identify a subgroup of non-responding patients for whom ineffective chemotherapy should be avoided.

Synopsis

Breast cancer is the most frequently diagnosed cancer in women. The indications for neoadjuvant chemotherapy are increasing. Early information on chemotherapy response is crucial and methods that predict the therapeutic effectiveness might avoid potentially ineffective chemotherapies in non-responding patients.     

Inadequacy of computed tomography in assessing patients with esophageal carcinoma after induction chemoradiotherapy

BACKGROUND: Induction chemoradiotherapy followed by surgery may improve survival of patients with esophageal carcinoma. Computed tomography (CT) has been used to evaluate the tumor response after completing induction chemoradiotherapy. The authors examined the ability of CT to evaluate the pathologic tumor response to induction therapy and to stage the tumor correctly. METHODS: Preinduction and postinduction chemoradiotherapy CT scans were reviewed retrospectively for 50 patients enrolled in a protocol of induction chemoradiotherapy followed by surgery. All studies were performed on third-generation or fourth-generation scanners. Radiographic response was determined using Eastern Cooperative Oncology Group solid tumor response criteria for bidimensional measurable disease. This was compared with the pathologic tumor response. CT-tumor (T) classification using the modified Tio scale was compared with the pathologic T classification. RESULTS: CT-T classification did not correlate with the pathologic stage (P = 0.09) or the pathologic tumor response (P = 0.22). The postinduction chemoradiotherapy CT accurately staged the T classification in 42% of patients but overstaged 36% of patients and understaged 20% of patients. CT had a sensitivity of 65%, a specificity of 33%, a positive predictive value of 58%, and a negative predictive value of 41% in evaluating the pathologic tumor response. CONCLUSIONS: CT is a poor diagnostic study tool for determining the pathologic tumor response or the pathologic disease stage after induction chemoradiotherapy in patients with esophageal carcinoma.     

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.     

Repeat 18F-FDG PET for monitoring neoadjuvant chemotherapy in patients with stage III non-small cell lung cancer

PURPOSE: The relevance of (18)F-FDG PET for staging non-small cell lung cancer (NSCLC), in particular for the detection of lymph node or distant metastases, has been shown in several studies. The value of FDG-PET for therapy monitoring in NSCLC, in contrast, has not yet been sufficiently analysed. Aim of this study was to evaluate FDG-PET for monitoring treatment response during and after neoadjuvant radiochemotherapy (NARCT) in advanced NSCLC. METHODS: Sixty-five patients with histologically proven NSCLC stage III initially underwent three FDG-PET investigations, during NARCT prior to initiating radiation, and post-NARCT. Changes of FDG-uptake in the primary tumour at two time-points during NARCT were analysed concerning their impact on long-term survival. RESULTS: The mean maximum FDG uptake (standardized uptake value, SUVmax) of the whole group decreased significantly during NARCT (SUVmax PET 1: 14.9+/-4.0, SUVmax PET 3: 5.5+/-2.4, p=0.004). The difference between initial FDG uptake (PET 1) and uptake after induction chemotherapy (PET 2) was found to be highly predictive for long-term survival patients which had a greater than 60% decreases in their SUV change had a significantly longer survival than those below this threshold (5-year-survival 60% versus 15%, p=0.0007). Patients who had a lower than 25% decrease in their SUV change had a 5-years-survival lower than 5%. Furthermore, the difference between initial FDG uptake (PET 1) and uptake after completion of the whole NARCT (PET 3) was predictive for survival when 75% was applied as cut-off (p=0.02). However, the level of significance was considerably lower. CONCLUSION: FDG-PET is suitable for therapy monitoring in patients with stage III NSCLC. The decrease of FDG uptake during induction chemotherapy is highly predictive for patient outcome.     

Improvement in preoperative staging of gastric adenocarcinoma with positron emission tomography

BACKGROUND: Positron emission tomography (PET) with 18- fluorodeoxyglucose (FDG) has been used to both detect and stage a variety of malignancies. The current study examined the value of PET for preoperative staging of gastric adenocarcinoma. METHODS: Sixty-eight patients (49 males and 19 females) with gastric adenocarcinoma, who were referred for preoperative FDG-PET scans, were enrolled in this study. The patients underwent spiral-computed tomography (CT) within 1 week of referral. The final diagnosis in all patients was made by histologic and surgical findings. For quantitative PET analysis, the regional tumor FDG uptake was measured by the standardized uptake value (SUV). RESULTS: For the primary tumor of a gastric adenocarcinoma, PET demonstrated an increased uptake in 64 of 68 patients (sensitivity, 94%), with a mean SUV of 7.0 (range, 0.9-27.7). A comparison of FDG uptake and clinicopathologic features showed significant association between FDG uptake and macroscopic type, tumor size, lymph node metastasis, histologic type, and TNM stage. The PET scan had a similar accuracy with that of CT for diagnosing local and distant lymph node metastases as well as peritoneal status. In assessing local lymph node status, however, PET had a higher specificity than CT (92% vs. 62%, P = 0.000). Moreover, PET had additional diagnostic value in 10 (15%) of 68 patients by upstaging 4 (6%) and downstaging 6 (9%) patients. PET combined with CT was more accurate for preoperative staging than either modality alone (66% vs. 51%, 66% vs. 47%, respectively; P = 0.002). CONCLUSIONS: FDG-PET improves the preoperative TNM staging of gastric adenocarcinoma. Based on its superior specificity, FDG-PET can facilitate the selection of patients for a curative resection by confirming a nodal status identified by CT.     

Radiation response non-invasively imaged by [18F]FDG-PET predicts local tumor control and survival in advanced oral squamous cell carcinoma

It is a major challenge to preoperatively identify patients who will profit from surgery of advanced oral cancer. In multimodality therapy, response to neoadjuvant radiation correlates to treatment success. Hence, for preoperative decisions, assessment of treatment response is required. Therefore, we analysed the prognostic significance of glucose metabolism after preoperative radiotherapy. [(18)F]FDG-PET investigations were performed for re-staging 35 patients after neoadjuvant radiotherapy (36Gy) immediately prior to tumor resection. Emission and transmission measurements were obtained and SUV's were calculated for the sites of maximum [(18)F]FDG-uptake. Subpopulations of "low" (SUV < 4) and "high" (SUV > or = 4) glucose metabolism were compared by univariate and multivariate survival analysis. 3-years survival was 80% in the "low" SUV group and 43% in the "high" SUV group. Post-irradiation [(18)F]FDG-uptake significantly predicts survival (P = 0.046) and local tumor control (P = 0.0017). High [(18)F]FDG-uptake was associated with an increased hazard of death (P = 0.037) and especially of local progress (P = 0.011) even when radical resection was performed. Thus, [(18)F]FDG-PET non invasively identified patients with poor prognosis whose indication for radical surgery has to be considered with caution.     

Value of 18F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in non-small-cell lung cancer for prediction of pathologic response and times to relapse after neoadjuvant chemoradiotherapy.

PURPOSE: To determine the value of combined positron emission tomography/computed tomography (PET/CT) during induction chemotherapy (CTx) followed by chemoradiotherapy (CTx/RTx) for non-small-cell lung cancer to predict histopathologic response in primary tumor and mediastinum and prognosis of the patient. EXPERIMENTAL DESIGN: Fifty consecutive patients with locally advanced non-small-cell lung cancer received induction therapy and, if considered resectable, proceeded to surgery (37 of 50 patients). Patients had at least two repeated 18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans either before treatment (t0) or after induction CTx (t1) or CTx/RTx (t2). Variables from the PET/CT studies [e.g., lesion volume and corrected maximum standardized glucose uptake values (SUV(max,corr))] were correlated with histopathologic response (graded as 3, 2b, or 2a: 0%, >0-10%, or >10% residual tumor cells) and times to failure. RESULTS: Primary tumors showed a percentage decrease in SUV(max,corr) during induction significantly larger in grade 2b/3 than in grade 2a responding tumors (67% versus 34% at t(1), 73% versus 49% at t(2); both P < 0.005). SUV(max,corr) at t(2) was significantly correlated with histopathologic response in tumors smaller than the median volume (7.5 cm(3); r = -0.54, P = 0.02). In the mediastinal lymph nodes, SUV(max,corr) values at t2 predicted an ypN0 status with a sensitivity and specificity of 73% and 89%, respectively (SUV(max,corr) threshold of 4.1, r = -0.54, P = 0.0005). Freedom from extracerebral relapse was significantly better in grade 2b/3 patients (86% at 16 months versus 20% in 2a responders; P = 0.003) and in patients with a greater percentage decrease in SUV(max,corr) in the primary tumor at t2 in relation to t0 than in patients with lesser response (83% at 16 months versus 43%; P = 0.03 for cutoff points between 0.45 and 0.55). CONCLUSIONS: SUV(max,corr) values from two serial PET/CT scans, before and after three chemotherapy cycles or later, allow prediction of histopathologic response in the primary tumor and mediastinal lymph nodes and have prognostic value.     

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.