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[Early evaluation using PET-FDG of the efficiency of neoadjuvant radiochemotherapy treatment in locally advanced neoplasia of the lower rectum].

BACKGROUND AND PURPOSE: Preoperative chemoradiation allows downstaging of locally advanced rectal cancer and in selected patients also a sufficient downsizing to ensure sphincter preservation. Selection of patients warranting a preoperative approach is improved by magnetic resonance imaging (MRI) which is able to define the involvement of mesorectal circumferential margin. Similarly it would be crucial to define the response to chemoradiation during the treatment but traditional morphologic imaging techniques may fail in differentiating neoplastic tissue from scarring. PET-FDG has been successfully used in the detection of metastatic colorectal cancer allowing imaging of deposits as small as 0.5 cm and may have a role in evaluating early response to chemoradiation. METHODS: In the present study, in patients with T3-T4 rectal cancer undergoing preoperative chemoradiation PET-FDG and flow cytometry analysis on endoscopic biopsy specimen have been performed before, during and after preoperative chemoradiation. RESULTS: Chemoradiation treatment has been successful in terms of downsizing and downstaging of the tumor. PET-FDG was able to demonstrate local response at only ten-fifteen days after the beginning of neoadjuvant therapy, also identifying non responding patients. CONCLUSIONS: FDG-PET may have a role in defining the response to chemoradiation and modulate the treatments strategy in patients with advanced rectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Preferred location for the development of esophageal adenocarcinoma within a segment of intestinal metaplasia.

BACKGROUND: Barrett's metaplasia is the predominant precursor for the development of esophageal adenocarcinoma. This precancerous lesion has become the focus of various surveillance programs aimed at detecting earlier and therefore potentially curable lesions. However, sampling error by missing invasive cancer lesions is a common problem. This study aimed to identify preferred locations within a segment of Barrett's mucosa for the development of esophageal adenocarcinoma. METHODS: The study group consisted of 213 patients with histologically proven esophageal adenocarcinoma. Of those, there were 134 cases of early cancer and 79 cases of locally advanced lesions. These patients received neoadjuvant chemotherapy. The frequency of intestinal metaplasia and the location of the tumor occurrence within the segment of intestinal metaplasia were assessed. RESULTS: Intestinal metaplasia was found in 83% of the early lesions and in 98% of the advanced tumors after neoadjuvant chemotherapy. In 82.2% of the cases, the tumor was located at the distal margin of the intestinal metaplasia in patients with early tumor manifestations. The remaining tumor mass after neoadjuvant therapy also was located predominantly at the distal margin of the segment of intestinal metaplasia (85% of the cases). CONCLUSIONS: The results demonstrate that almost all adenocarcinomas of the esophagus are based on the development of a segment of intestinal metaplasia. The distal margin of Barrett's mucosa seems to be the most vulnerable location for the development of invasive cancer.

Adenocarcinoma↗

Pulmonary Langerhans cell histiocytosis associated with lingual carcinoma.

A 57-year-old man who was a heavy smoker was admitted to our hospital for further evaluation of abnormal shadows on a chest X-ray film. Chest radiography and a computed tomography (CT) scan revealed nodular lesions and multiple thin-walled cysts in both lungs. Histopathological examination of one of these cystic lesions showed that the predominant cellular population was Langerhans cells, with the cytoplasm testing positive for S-100 protein and the cell membrane showing a positive reaction for CD1a. The pathological diagnosis was pulmonary Langerhans cell histiocytosis (LCH). A lingual carcinoma that had been detected simultaneously was treated with neoadjuvant therapy and the patient was advised to stop smoking. However, only limited improvement was seen on follow-up chest CT. In view of this, a radical resection of the lingual carcinoma was performed. There was a subsequent dramatic improvement in the pulmonary LCH. Langerhans cells may play a role in the immune response to tumors. In this patient, we suggest the possibility that both the habitual smoking and the lingual carcinoma may have contributed to the development of pulmonary LCH.

Antineoplastic Combined Chemotherapy Protocols↗

[Larynx-preserving pharyngoesophagectomy in the treatment of cancer of the pharyngoesophageal junction].

UNLABELLED: Pharyngo-laryngo-esophagectomy has been the sole surgical option in the management of advanced tumors arising from the pharyngoesophageal junction. This operation is associated with high morbidity, mortality and poor quality of life due to loss of larynx. The aim of the author was to achieve a reduction in tumor size by means of neoadjuvant chemoradiotherapy and so to make the tumor amenable to a larynx preserving operation avoiding pharyngo-laryngo-esophagectomy. Between 1. January 1998 and 31. December 1999, 11 consecutive patients with advanced cancer of pharyngo-esophageal junction were treated with neoadjuvant chemoradiotherapy (carboplatin, 5-fluorouracil, 30-35 Gy telecobalt irradiation). The tumor regressed in all cases and moreover, in 6 patients a larynx preserving pharyngo-esophagectomy could be carried out. This operation consists of total esophagectomy, resection of posterior pharynx wall and Akiyama-type gastric pull up with side-to-side pharyngo-gastrostomy. All 6 patients recovered. In 2 cases after neoadjuvant therapy the tumor disappeared from the cervical esophagus and so that a pharyngo-laryngectomy and free jejunum transfer could be performed. 3 other patients remained irresectable due to lymph node metastases. CONCLUSION: Larynx preserving pharyngo-esophagectomy is a safe operation by means of which the larynx can be preserved even in those patients whose tumor is located at the level of pharyngo-esophageal junction, on the posterior wall of the pharynx.

Aged↗

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus.

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.

Aged↗

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans↗

Breast conservation after neoadjuvant chemotherapy.

BACKGROUND: Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients. METHODS: The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics. RESULTS: Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the existence of a circumscribed lesion on mammography. CONCLUSIONS: The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.

Adult↗

Neoadjuvant gemcitabine and cisplatin followed by radical surgery in (bulky) squamous cell carcinoma of cervix stage IB2.

OBJECTIVES: This study aimed to evaluate the efficacy and toxicity of gemcitabine in combination with cisplatin as neoadjuvant therapy in patients with cervical carcinoma stage IB2. PATIENTS AND METHODS: Chemotherapy-naive patients with histologic diagnosis of squamous cell cervical carcinoma staged as IB2 were treated with 2 cycles of cisplatin (70 mg/m(2) on day 1) and gemcitabine (1000 mg/m(2) on days 1 and 8), given every 21 days. After chemotherapy, patients underwent radical hysterectomy and pelvic lymphadenectomy. Patients judged to have a non-resectable disease were treated with standard pelvic radiation. RESULTS: Between September 2000 to March 2004, 28 patients were enrolled in the study, of which 27 were evaluable for efficacy and toxicity. The mean age was 39 years (30-55). The overall clinical response rate was 88.9% (24/27), with complete response (CR) in 9/27 patients (33.3%) and partial response in 15/27 patients (55.5%). Three patients (11.1%) did not respond and nobody progressed. A pathological CR was noted in 2 of 24 patients who underwent radical surgery. The 3 non-responding patients were subsequently treated with radiation and achieved CR. Grades 3 or 4 neutropenia, anemia, or thrombocytopenia was observed in 18.5%, 7.4%, and 3.7% patients respectively. Non-hematological toxicity was mild except grade 3 nausea/vomiting in 18.5% patients. At median follow-up time of 36.7 months (range 7-51 months), the 3-year survival was 88.9%. CONCLUSION: Neoadjuvant treatment with gemcitabine/cisplatin combination for patients with cervical cancer (stage IB2) appears encouraging, with manageable and acceptable toxicity profile.

Adult↗

Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: Pancreatic cancer remains highly lethal. Previous attempts with neoadjuvant therapy in this disease have been inconclusive, but a potential for benefit exists. We conducted a phase II trial of dose-intense docetaxel and gemcitabine followed by twice-weekly gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. METHODS: Patients with stage I to III disease were eligible. Docetaxel 65 mg/m(2) intravenously over 1 hour and gemcitabine 4000 mg/m(2) given intravenously over 30 minutes were given on days 1, 15, and 29. On day 43, radiotherapy was begun at 50.4 Gy with gemcitabine 50 mg/m(2) intravenously over 30 minutes twice weekly for 12 doses. After treatment, patients were considered for resection. RESULTS: Twenty-four assessable patients were recruited onto the trial. All but one patient completed a full 12 weeks of therapy. Grade 3 and 4 hematological and nonhematological toxicities were common but manageable, and neutropenic fever did not occur. No patient had local tumor progression. Twelve patients (50%) responded by Response Evaluation Criteria in Solid Tumors Group (RECIST) criteria, including one radiographic complete response. Seventeen patients underwent resection after therapy. Margin-negative resections were performed in 13 patients, including 9 patients whose disease was borderline or unresectable before treatment. A treatment effect was seen in all resection specimens. There have been no local recurrences of tumor, and several patients remain alive without evidence of disease. CONCLUSIONS: Docetaxel/gemcitabine followed by gemcitabine/radiotherapy is active in the treatment of pancreatic adenocarcinoma, with manageable toxicity. Tumor downstaging occurs in some patients to allow complete resection. Further investigation of this regimen is warranted.

Adenocarcinoma↗

Prevalence and significance of prominent mucin pools in the esophagus post neoadjuvant chemoradiotherapy for Barrett's-associated adenocarcinoma.

Occasionally, patients with Barrett's-associated adenocarcinoma who received preoperative chemoradiotherapy (chemrad) show prominent mucin pools in their resection specimen, but the prognostic significance of this finding has never been investigated. The purpose of this study was to evaluate the clinical and pathologic features, and prognostic significance, of prominent mucin pools in 21 patients identified from a cohort of 192 consecutive cancer patients (prevalence rate, 10.9%) who had an esophagectomy (post-chemrad) for adenocarcinoma. The clinical and pathologic features and follow-up data were evaluated in 21 patients with adenocarcinoma of the esophagus and with prominent mucin pools (male-to-female ratio, 21:0; mean age, 61 years) and compared with a control group of 19 consecutive chemrad-treated and stage-matched esophageal adenocarcinoma patients who had either minimal microscopic (9 cases) or no (10 cases), residual disease present in their resection specimen (male-to-female ratio, 18:1; mean age, 62 years). Of the 21 study patients, 7 (33%) had acellular mucin pools with no residual tumor, 7 (33%) showed rare isolated tumor cells within mucin pools, and 7 (33%) had acellular mucin pools with microscopic foci of residual adenocarcinoma in tissue adjacent to, but not within, mucin pools. In total, 2 cases (9%) showed mucin pools limited to the submucosa, 5 (24%) showed involvement of the muscularis propria, and 14 (67%) showed mucin pools within the muscularis propria and adventitia. Four cases (19%) showed involvement of the radial resection margin with acellular mucin pools. Thirteen study patients (62%) contained acellular mucin pools within regional lymph nodes. A significantly higher proportion of patients with prominent mucin pools had mucinous adenocarcinoma prior to neoadjuvant therapy, compared with control patients without mucin pools (12 of 21 (57%) vs. 1 of 19 (5%), P < 0.001). Upon follow-up (mean, 27 months; range, 5-84 months), none of the study patients with prominent mucin pools died of disease (0%), in comparison to 5 of 19 (26%) control patients (mean follow-up, 27 months; range, 3-64 months) (P = 0.02). None of the patients who had acellular mucin pools involving the radial margin developed recurrence or metastasis or died of disease. Prominent mucin pools in resection specimens from patients with Barrett's esophagus-associated adenocarcinoma who received preoperative chemrad are associated with mucinous tumors and are not associated with poor survival, even when acellular mucin pools involve the radial margin, and, thus, should not be interpreted as evidence of residual viable adenocarcinoma.

Adenocarcinoma↗

[Neoadjuvant treatment in surgery of esophageal cancer].

We conducted a prospective study on neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. Thirty-two patients, 30 men, 2 women, mean age 56.2-8.9 years, with resectable squamous celi carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) were included. Chemotherapy, CDDP (80 mg/m2: D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and 1-folinic acid (200 mg/m2, DI-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg Injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelests, mucosite's) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n = 18), persistent microscopic residues (n = 4), or not significant modification (n = 4). Survival at 1, 3, and 5 years was 82, 47, and 47% and disease-free survival was 77, 47, and 47% respectively. This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 5-year survival reached 47%, a very high rate in our experience.

Antineoplastic Combined Chemotherapy Protocols↗

An integrated view of aromatase and its inhibition.

Aromatase inhibition has become a major treatment strategy for postmenopausal women with oestrogen-dependent breast cancer. Its optimal application is, however, dependent upon (i) the accurate identification of cancers which are ultimately dependent upon the activity of the aromatase enzyme, (ii) the use of the best method/inhibitor by which to blockade aromatase activity. The single best predictor of response to aromatase inhibitors is the presence of tumour oestrogen receptors; receptor-negative cancers rarely respond whereas those with high levels seem particularly likely to benefit. However, there is a need for additional discriminatory markers. The use of microarray technology coupled with neoadjuvant therapy is likely to yield promising candidate genes. The finding that, amongst peripheral tissues, the tumour itself may have high activity has led to the suggestion that the tumour aromatase measurements may be predictive; however, in situ studies and the lack of robust assays for tumour aromatase suggest that tumour aromatase may not be an influential marker. Whilst drugs such as anastrozole, exemestane, formestane and letrozole are all effective and specific inhibitors of aromatase, they differ in structure, potency and mechanism of action. Thus, differential sensitivity of tissues/tumours and non-cross resistance mean inhibitors are not equivalent and individual agents may have differing roles according to the setting in which they will be used. Aromatase inhibitors have evolved as key endocrine agents in the treatment of breast cancer. They offer the promise of rational treatment management based on the accurate identification of individual cohorts of tumours responsive to specific drugs.

Aromatase↗

Long-term results in patients with T2-3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery.

BACKGROUND: Local excision after radiotherapy for node-negative low rectal cancer may be an alternative to radical excision. This study evaluated the results of local excision in patients with small (less than 3 cm in diameter) T2 and T3 distal rectal tumours following neoadjuvant therapy. METHODS: One hundred patients with rectal cancer (54 uT2 and 46 uT3 uN0 tumours) were enrolled. All patients underwent preoperative radiotherapy followed by local excision by means of transanal endoscopic microsurgery. RESULTS: Definitive histological examination revealed nine pT1, 54 pT2 and 19 pT3 tumours. A complete response (R0) or microscopic residual tumour (R1mic) was found in three and 15 patients respectively. Minor complications occurred in 11 patients and major complications in two. At a median follow-up of 55 (range 7-120) months, the local failure rate was 5 per cent and metastatic disease was found in two patients. The cancer-specific survival rate at 90 months' follow-up was 89 per cent, and the overall survival rate 72 per cent. Salvage abdominoperineal resection was performed in three patients, two of whom were disease free at 15 and 19 months. CONCLUSION: Treatment of small uT2 and uT3 uN0 rectal cancers with preoperative high-dose radiotherapy followed by transanal endoscopic microsurgery is an acceptable alternative to conventional radical resection.

Adult↗

The prognostic value of angiogenesis and metastasis-related genes for progression of transitional cell carcinoma of the renal pelvis and ureter.

PURPOSE: We reported previously that angiogenesis evaluated by intratumor microvessel density (MVD), expression of such angiogenic factors as vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF), and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify patients with advanced transitional cell carcinoma (TCC) of the bladder for whom chemotherapy and cystectomy will be unsuccessful. In the present study, we evaluated the significance of the M:E ratio as a predictor for prognosis for patients with TCC in the upper urinary tract (TCC-UUT). EXPERIMENTAL DESIGN: We evaluated MVD by immunohistochemistry and the expression of angiogenic and metastasis-related factors by in situ hybridization in 55 nephroureterectomy specimens from patients who received no neoadjuvant therapy. The expression of angiogenesis, angiogenic and metastasis-related factors, and clinicopathological characteristics were evaluated for their correlation with metastasis, recurrence, and disease prognosis. RESULTS: We found that tumor grade and pathological stage were important predictors for metastasis and survival in these patients. The expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2) and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis. Moreover, lower expression levels of E-cadherin were associated with fewer recurrences in the urinary bladder. Multivariate analysis indicated that the M:E ratio and E-cadherin expression were independent prognostic factors for disease progression and intravesical recurrence, respectively. CONCLUSION: We suggest that the M:E ratio and E-cadherin expression may be targets for novel therapeutic strategies.

Adult↗

The diaphragmatic flap: A multiuse material in thoracic surgery.

BACKGROUND: The use of diaphragmatic pedicle flaps for reconstructive procedures in thoracic surgery is not very popular. Nevertheless, it provides considerable advantages. METHODS: Our experience covers 10 years (1987-1997) with a total of 25 patients in whom the diaphragmatic flap was used for different purposes. In 6 patients we used the diaphragmatic flap to protect the bronchopleural fistula at its early onset, which was not beyond 12 hours from the clinical diagnosis. We performed prophylactic suture protection after neoadjuvant therapy in 9 high-risk patients who underwent pneumonectomy and in 2 who underwent sleeve lobectomy. Postpneumonectomy pericardial defect repair was performed in 4 patients. In another 4 patients the diaphragmatic flap was used after spontaneous (n = 2) and iatrogenic (n = 2) lesions of the esophagus after 24 to 72 hours. RESULTS: No perioperative mortality was recorded. Complications were mainly related to the severe preoperative conditions of the patients: arrhythmia, respiratory insufficiency, and empyema. We report only 2 cases of minimal persistent bleeding from the chest tube, which spontaneously ceased. For those patients who survived for more than 1 year (n = 11), no diaphragmatic hernias were recorded. Bronchopleural fistulas and pericardial defects healed in all instances. The diaphragmatic flap was also effective in bronchopleural fistula. A late fistula caused by cancer relapse at the bronchial stump developed in only one patient. Excellent repair was achieved in all patients with esophageal lesions. CONCLUSIONS: We conclude that the diaphragmatic flap can be considered a practical, safe, and redundant material particularly indicated for defect or fistula closure and for suture line protection in the thoracic cavity.

Adult↗

Traditional versus up-front [18F] fluorodeoxyglucose-positron emission tomography staging of non-small-cell lung cancer: a Dutch cooperative randomized study.

PURPOSE: We investigated whether application of positron emission tomography (PET) immediately after first presentation might simplify staging while maintaining accuracy, as compared with traditional strategy in routine clinical setting. METHODS: At first presentation, patients with a provisional diagnosis of lung cancer without overt dissemination were randomly assigned to traditional work-up (TWU) according to international guidelines or early PET followed by histologic/cytologic verification of lesions, or imaging and follow-up. Patients with [18F] fluorodeoxyglucose (18FDG) -avid, noncentral tumors without suspicion of mediastinal or distant metastases on PET proceeded directly to thoracotomy. Follow-up in presumed benign lesions was at least 12 months. In patients treated with surgery or neoadjuvant therapy, the quality of staging was measured by comparing the clinical stage to the final stage (combination of peroperative staging and 6 months of follow-up). To investigate test substitution, we analyzed the number of (non)invasive tests to achieve clinical TNM staging, and its associated costs. RESULTS: Between 1999 and 2001, 465 patients (233 TWU, 232 PET) were enrolled at 22 hospitals. The mean (standard deviation) number of procedures to finalize staging was equal in the TWU arm and the PET arm: 7.9 (2.0) v 7.9 (1.9), P = .90, respectively. Mediastinoscopies occurred significantly less often in the PET arm. Agreement between clinical and final stage was good in both arms (kappa = .85 v .78; P = .07). Costs did not differ significantly. CONCLUSION: Up-front 18FDG-PET in patients with (suspected) lung cancer does not reduce the overall number of diagnostic test, but it maintains quality of TNM staging with the use of less invasive surgery.

Aged↗

Neoadjuvant chemotherapy with gemcitabine and cisplatin in stage IIIA/B non-small cell lung cancer.

PURPOSE: We studied cisplatin plus gemcitabine as induction (neoadjuvant) therapy in patients with stage III non-small cell lung cancer (NSCLC) to assess its objective remission rate, resectability, survival, and toxicity. PATIENTS AND METHODS: Patients with stage III NSCLC received 2 cycles of gemcitabine 1250 mg/m2 on days 1, 8, and 15, plus cisplatin 100 mg/m2 on day 2. Subsequently, patients were assigned to local therapy--surgery or radiotherapy. RESULTS: Twenty-nine eligible patients (male/female: 21/8) with a median age of 59 years (range, 43-71 years) were enrolled between October 1996 and February 1999. A total of 80 cycles were given, with a median of 3 per patient (range, 1-4 cycles). Overall, toxicities were mild; only one patient had febrile neutropenia, and there were no grade 4 non-hematological toxicities. There was one toxic death following afebrile grade 4 neutropenia. Overall clinical response rate (2 complete responses [CRs] + 16 partial responses [PRs]) was 62% (95% CI, 45%-79%); 10 patients had stable disease and none progressed; one patient was not evaluable. Eight of the 18 operated patients had pathological response: 1 CR and 7 downstagings to N(-); 14 patients were resected. Median survival was 17 months (95% CI, 13-21 months), with 1-year and 2-year actuarial survival rates of 61% and 29%, respectively. CONCLUSIONS: Gemcitabine plus cisplatin is a very active and well-tolerated induction regimen in stage III NSCLC. Comparative studies with other standard regimens are warranted.

Adult↗

Endorectal ultrasound in the preoperative evaluation of rectal cancer.

For rectal cancer, the decisions about neoadjuvant therapy, radical resection, or local excision depend on accurate preoperative staging. Multiple modalities are available to stage rectal cancer, including digital rectal examination, computed tomography, magnetic resonance imaging (MRI), and endorectal ultrasound (ERUS). Digital rectal examination accuracy varies from 58% to 88% for depth of penetration. Computed tomography accuracy varies from 53% to 94% for depth of penetration and from 54% to 70% for lymph node metastases. Magnetic resonance imaging accuracy varies from 66% to 92% for depth of penetration and from 60% to 90% for lymph node metastases. Endorectal ultrasound varies from 62% to 92% for depth of penetration and from 64% to 88% for lymph node metastases. In all radiologic modalities, overstaging and understaging occurs. Endorectal ultrasound has the advantage of being portable and often office-based, requiring only minimal preparation and is well tolerated by the patient. Although MRI with the use of an endorectal coil may have a slightly higher accuracy for detecting lymph nodes, ERUS has been shown to be the most accurate method for the determination of the depth of wall penetration, and is comparable for lymph node metastases. Interpretation varies with operator experience. Three-dimensional (3D) ERUS may further improve staging accuracy. Endorectal ultrasound is an accurate method to preoperatively stage rectal cancers. Although operator-dependent, it can be readily performed at the time of patient evaluation with minimal preparation or patient discomfort. We are prospectively evaluating modifications to the current staging system and the use of 3D ERUS.

Endosonography↗