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Effect of nutrition staging on treatment delays and outcome in Stage IV neuroblastoma.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life-table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P less than 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P less than 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.

Abdominal Neoplasms↗

Comparison of outcome between clinically staged, unresected superior sulcus tumors and other stage III non-small cell lung carcinomas treated with radiation therapy alone.

Several studies suggest that patients with non-small cell lung carcinoma (NSCLC) of the superior sulcus fare better after radiation therapy than those patients with comparable tumors at other thoracic sites. There is limited data on stage-by-stage comparisons between patients with superior sulcus tumors (SST) and non-SST (NSST). Thirty patients had SST among 656 patients with American Joint Committee on Cancer clinically staged IIIA (n = 389) and IIB (n = 267) primary NSCLC who received definitive once-daily radiation therapy. The median patient age, sex ratio, histologic findings, grade, weight loss, and performance status were similar for SST and NSST. Minimum follow-up was 24 months, with 88% of patients followed until death. The survival of patients with SST (median, 10.3 months) was similar to that of patients with tumors at other pulmonary sites (median, 10.8 months; P = 0.39). Survival for favorable patients with performance status 0 to 1 and weight loss of 5% or less was comparable between patients with SST (median, 15.0 months) and NSST were similar for patients with SST and NSST (P = 0.48). The brain was the site of first failure in 20% of patients with SST and 10% of patients with NSCLC at other sites (P = 0.10). The lack of apparent difference in outcome of comparably staged patients with SST and NSST treated with radiation alone may have significant therapeutic implications.

Adult↗

Four cycles of chemotherapy and regional radiation therapy for clinical early-stage and intermediate-stage Hodgkin's disease.

To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.

Adolescent↗

High-dose chemotherapy followed by locoregional irradiation improves the outcome of patients with international neuroblastoma staging system Stage II and III neuroblastoma with MYCN amplification.

BACKGROUND: The objective of this study was to determine whether systemic and regional, intensified treatment can improve the outcome of children who present with a localized neuroblastoma (NB) with MYCN amplification (MNA). METHODS: Between 1990 and 2000, 610 children with localized NB were included in the Localized Neuroblastoma 90 (NBL 90) and NBL 94 study from the French Society of Pediatric Oncology. Among them, 32 children had MNA with Stage II or III NB. During the first period of the study, 20 children (Group A) received postoperative conventional chemotherapy (CT) and/or radiotherapy (RT), depending on each patient's postoperative status. Subsequently, because of a high recurrence rate, the next 12 children (Group B) were given postoperative high-dose CT (HDC) (busulfan and melphalan) with stem cell rescue (SCR) followed by RT in addition to conventional postoperative CT. RESULTS: The two groups were comparable with regard to prognostic factors (age, location of the primary lesion, International Neuroblastoma Staging System stage, lymph node invasion) and response to preoperative CT. The 6-year overall survival rate was significantly different between the two groups 25% +/- 10% in Group A vs. 83% +/- 11% in Group B; P = 0.004). CONCLUSIONS: Postoperative intensification treatment with HDC, SCR, and locoregional RT resulted in higher survival rates when compared with standard treatment alone and should be considered in the treatment plan for children who are diagnosed with Stage II or III NB and MYCN amplification.

Adolescent↗

Simultaneous combination radiotherapy and multidrug chemotherapy for stage III and stage IV squamous cell carcinoma of the head and neck.

Combined simultaneous radiotherapy and multidrug chemotherapy have been utilized in an attempt to eradicate or shrink tumors of the head and neck area in advanced stages to allow subsequent surgical extirpation. Thirty-six patients (1 stage II; 11 stage III; 24 stage IV; 1 unknown primary) were treated with simultaneous radiotherapy and fractionalized doses of bleomycin, adriamycin, and 5-fluorouracil. Thirty of 36 patients completed the treatment schedule. Twenty-nine of 30 (97%) had a 75% or greater response to treatment; 20/30 (66%) had 100% response; 9/30 (30%) had 75% response; and 1/30 had 50% response. Of the 30 patients completing the regimen, 19/30 (63%) are alive three to 27 months later, and 12 (40%) of these have no evidence of disease. Six patients died within four months of initiation of therapy, mostly from complications of their disease. This treatment regimen appears effective in the control of locoregional disease or to produce enough shrinkage of tumor to allow subsequent surgical extirpation.

Adult↗

Hydroxyurea plus pelvic irradiation versus placebo plus pelvic irradiation in nonsurgically staged stage IIIB cervical cancer.

Twenty-five patients with FIGO stage IIIB carcinoma of the cervix were entered into a prospective, double-blinded randomized study to evaluate the possible radiation potentiating properties (i.e., improved survival) of the S phase cell cycle specific inhibitor of DNA synthesis hydroxyurea (H). In contrast to our previous randomized trial of patients with FIGO stage IIIB carcinoma of the uterine cervix who were documented to be without paraaortic lymph node metastasis by pretherapy staging paraaortic lymphadenectomy [Piver et al.: J Surg Oncol 35: 129-134, 1987], these patients either refused surgical staging or, because of medical conditions, could not undergo pretherapy paraaortic lymphadenectomy. Patients were to receive 6,000 cGy/6 weeks to the pelvis by megavoltage radiation therapy followed by 2,500 cGy to point A by intracavitary and vaginal radium/cesium. The median pelvic cGy for the Hu patients was 5,967 cGy and for the placebo patients 6,013 cGy. Leukopenia (WBC less than 2,500/mm3) significantly increased in patients given hydroxyurea as compared with those given placebo (P less than 0.0001). There was no statistically significant difference relative to anemia, thrombocytopenia, radiation skin reactions, diarrhea, or radiation induced complications requiring surgical correction. The estimated 5 year disease-free interval was 54% for the hydroxyurea patients (median not reached) and 18% for the placebo patients with a median of 11 months. Because of these results, those of our previous reports, and those of the Gynecologic Oncology Group, we believe that hydroxyruea plus pelvic radiation should be the standard against which new potential radiation sensitizers are tested.

Adult↗

Analysis of allelic imbalance on chromosome 17p13 in stage I and stage II epithelial ovarian cancers.

OBJECTIVES: To determine whether there is evidence for allelic imbalance (AI) on chromosome 17p13 in early-stage epithelial ovarian tumors. METHODS: Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs) on chromosome 17p13 by polymerase chain reaction (PCR) amplification. RESULTS: Sixteen of 29 (55%) tumors showed AI at one or more loci, including 7 of 29 (24%) tumors that showed distinct regions of AI. AI at p53 was present in only 9 of 25 (36%) informative tumors. A region of AI, defined by marker D17S654, close to candidate genes OVCA1 and OVCA2, was identified distal to p53 and occurred in 11 of 23 (48%) informative tumors. This region of AI also extended more distal to this locus, and included marker D17S695 where AI occurred in 11 of 26 (42%) informative tumors. Microsatellite instability was observed in 2 of 29 tumors. CONCLUSIONS: This study supports the presence of at least one tumor suppressor gene on chromosome 17p13 distal to p53 that is involved in the early development of epithelial ovarian cancer. This study also suggests that the molecular analysis of early-stage epithelial ovarian cancers can provide important information on the genetic etiology of ovarian cancers.

Alleles↗

Laparoscopic staging compared with imaging techniques in the staging of advanced cervical cancer.

OBJECTIVE: We evaluated the evidence of laparoscopy for decision regarding treatment options in advanced cervical cancer patients. METHODS: One hundred nine consecutive patients with cervical cancer FIGO stage Ib2 and higher underwent laparoscopic staging of the extent of disease. Laparoscopic and histopathologic evaluation of tumor involvement of the paraaortic and pelvic lymph nodes, wall of the bladder, and rectal pillar was compared with preoperative findings of MRI and/or CT. RESULTS: Paraaortic lymphadenectomy was performed in 101 (92.7%) patients and 21 (19.3%) patients had positive paraaortic lymph nodes. Pelvic lymphadenectomy was performed in 75 (68.8%) patients and 20 (26.7%) patients had positive pelvic lymph nodes. In 11 patients (11.5%) infiltration of the bladder and in 6 patients (6.25%) infiltration of the rectal pillar or cul-de-sac was found. Intraoperative complications associated with laparoscopic staging occurred in 3.7% of patients. The negative predictive value for the evaluation of paraaortic or pelvic lymph nodes, the bladder wall, rectal pillar, and cul-de-sac ranged from 73% (CT for pelvic lymph nodes) to 96% (MRI for bladder wall). Lack of information about the extent of disease was adjusted on the basis of laparoscopic findings in 24 (22%) patients and improved treatment plans. CONCLUSION: Laparoscopic staging of patients with advanced cervical cancer is accurate, associated with low morbidity, and helps to adjust treatment according to extent of disease.

Adult↗

Lymphography and computed tomography in staging nonseminomatous testicular cancer: limited detection of early stage metastatic disease.

The efficacy of lymphography and computed tomography (CT) in staging nonseminomatous testicular cancer was analyzed in 41 patients. Retroperitoneal lymphadenectomy in 30 patients with early tumor stage revealed 56% sensitivity, 90% specificity, and 80% overall accuracy for lymphography; CT was less accurate (44% sensitivity, 81% specificity, 70% overall accuracy). The presence of advanced disease in 11 patients was depicted equally by lymphography and CT, but CT better demonstrated the anatomic extent of the metastases. CT is valuable for discriminating between advanced and early tumor stages; the similar inaccuracy of lymphography in early disease militates against its routine and complementary use; retroperitoneal lymphadenectomy then remains the only accurate staging modality.

Adolescent↗

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures.

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.

Adult↗

Prostate cancer: comparison of local staging accuracy of pelvic phased-array coil alone versus integrated endorectal-pelvic phased-array coils. Local staging accuracy of prostate cancer using endorectal coil MR imaging.

To compare the visibility of anatomical details and prostate cancer local staging performance of pelvic phased-array coil and integrated endorectal-pelvic phased-array coil MR imaging, with histologic analysis serving as the reference standard. MR imaging was performed in 81 consecutive patients with biopsy-proved prostate cancer, prior to radical prostatectomy, on a 1.5T scanner. T2-weighted fast spin echo images of the prostate were obtained using phased-array coil and endorectal-pelvic phased-array coils. Prospectively, one radiologist, retrospectively, two radiologists and two less experienced radiologists working in consensus, evaluated and scored all endorectal-pelvic phased-array imaging, with regard to visibility of anatomical details and local staging. Receiver operator characteristics (ROC) analysis was performed. Anatomical details of the overall prostate were significantly better evaluated using the endorectal-pelvic phased-array coil setup (P<0.05). The overall local staging accuracy, sensitivity and specificity for the pelvic phased-array coil was 59% (48/81), 56% (20/36) and 62% (28/45), and for the endorectal-pelvic phased-array coils 83% (67/81), 64% (23/36) and 98% (44/45) respectively, for the prospective reader. Accuracy and specificity were significantly better with endorectal-pelvic phased-array coils (P<0.05). The overall staging accuracy, sensitivity and specificity for the retrospective readers were 78-79% (P<0.05), 56-58% and 96%, for the endorectal-pelvic phased-array coils. Area under the ROC curve (Az) was significantly higher for endorectal-pelvic phased-array coils (Az=0.74) compared to pelvic phased-array coil (Az=0.57), for the prospective reader. The use of endorectal-pelvic phased array coils resulted in significant improvement of anatomic details, extracapsular extension accuracy and specificity. Overstaging is reduced significantly with equal sensitivity when an endorectal-pelvic phased-array coil is used.

Adult↗

Survival of nonsurgically staged patients with negative lymphangiograms who had Stage IIB carcinoma of the cervix treated by pelvic radiation plus hydroxyurea.

Twenty patients with Stage IIB carcinoma of the cervix who did not undergo pretherapy para-aortic lymphadenectomy, but who had negative preradiation therapy lymphangiograms, were treated with pelvic radiation plus hydroxyurea. Patients received a median of 5020 rads of pelvic radiation plus 4000 rads of radium to point A. During radiation therapy and for a total of 12 weeks, patients received hydroxyurea administered at a dose of 80 mg/kg of body weight every 3 days if the white blood cell count was greater than or equal to 2,500/mm3 and platelets were greater than or equal to 75,000/mm3. The median follow-up time was 28 months (6 to 83 months). The estimated 5-year survival rate was 92%. Seventeen patients are alive with no evidence of disease (median, 28 months); one died of intercurrent disease with no evidence of disease (17 months); one is alive with no evidence of disease after recurrence (18 months); and one died of cervical cancer (22 months). The survival rate of patients with nonsurgically staged negative pretherapy lymphangiograms who had Stage IIB cervical cancer treated by pelvic radiation therapy plus hydroxyurea approximated the improved survival rate reported for patients with negative pretherapy para-aortic lymphadenectomy who were treated with pelvic radiation therapy plus hydroxyurea. Both studies would suggest that pelvic radiation plus hydroxyurea improves the rate of survival in patients with Stage IIB cervical cancer.

Adult↗

Stage A2 prostatic carcinoma: should staging system be reclassified?

Seventy patients with clinically localized prostatic carcinoma were studied for histologic differentiation of primary tumor and the incidence of lymph node metastasis. Also the urologic literature was reviewed regarding the survival of such patients under similar treatment. The results indicate that clinically staged A2 tumors are more aggressive biologically than tumors staged as B1, reaffirming the need for a change in the current staging system. The authors propose reclassification of clinically unsuspected, diffuse carcinoma from the A to the B2 stage.

Adenocarcinoma↗

Comparing clinical staging plus transrectal ultrasound with surgical-pathologic staging of prostate cancer.

Twenty-five men with histopathologic diagnosis of prostatic adenocarcinoma were staged utilizing traditional staging modalities and transrectal ultrasound of the prostate (TRUSP). A comparison was then done with surgical-pathologic stage. TRUSP accurately predicted the local extent of disease in 84 percent of patients, while digital rectal examination understaged in 64 percent of patients. TRUSP is a valuable adjunct to staging prostate cancer prior to definitive therapy.

Adenocarcinoma↗

Clinical stage I adenocarcinoma of the endometrium--analysis of recurrences and the potential benefit of staging lymphadenectomy.

Two hundred forty-eight consecutive patients with clinical Stage I adenocarcinoma of the endometrium were seen between 8/77 and 8/88. Twenty-one were medically not operable and eleven others had papillary serous tumors. The remaining 216 were managed by a consistent operative protocol except that routine preoperative cesium was discontinued after 12/83. Patients received postoperative pelvic radiation on the basis of the depth of invasion, extrauterine pelvic disease, and/or cervix involvement. No patient underwent a pelvic lymphadenectomy. Only palpably suspicious nodes were removed. Twenty-one of these two hundred sixteen patients developed a recurrence. These 21 cases are analyzed for the probability of a staging lymphadenectomy having prevented their recurrence. Median follow-up of all 216 patients is 61 months with a mean time to recurrence of 26.5 months. No patient was lost to follow-up. Patients who recurred are analyzed by grade, depth of invasion, surgical stage, time to recurrence, site of recurrence, survival, protocol breaks, and frozen section discrepancies. No patient recurred on the pelvic side-wall. All patients found to have positive para-aortic nodes have died. No patient who received vaginal and/or pelvic radiation recurred in the pelvis. We conclude that staging lymphadenectomy would not have improved the outcome for these patients.

Adenocarcinoma↗

Value of computed tomography in staging the primary lesion (T-staging) of nasopharyngeal carcinoma (NPC): an analysis of 54 patients with special reference to the parapharyngeal space.

CT scans of the nasopharynx and the base of skull were performed in 54 patients with histologically proven NPC. The CT findings are compared to those obtained by routine clinical examination. In this series, involvement of the parapharyngeal spaces was found by CT scan in 61% (33/54) of patients, which is impossible to assess by clinical means. Intracranial invasion was demonstrated by CT scan with intravenous contrast enhancement in five patients. CT is more sensitive in showing the erosion of skull base than X ray film. CT scans demonstrated 17% (5/30) of bony invasion in X ray negative patients. Clinical examination showed one involved wall in nine patients; CT scan discovered involvement of two or more walls in five (55%) of these nine. Routine clinical examination discovered extra-nasopharyngeal extensions in 34 locations, whereas CT scans discovered 106, a ratio of 1:3.1. The common sites of extra-nasopharyngeal extension detected by CT scan are: parapharyngeal space, intracranial invasion, sphenoidal sinus, orbit, ethmoidal sinus, maxillary antrum, oropharynx and the nasal cavity. In T-staging of NPC, 55% (6/11) of clinical T2 lesions are up-staged by CT. Thirty-six percent (4/11) of clinical T3 lesions were also up-staged. However, 94% (17/18) of clinical T4 lesions remained unchanged. Only 6% (1/18) of clinical T4 lesions were down-staged.

Bone and Bones↗

Computed tomography in nasopharyngeal carcinoma: Part I: T-stage conversion with CT-staging.

Two hundred seventeen consecutive patients were treated with radiotherapy alone, with curative intent, from 1970 to 1985 at the Radiotherapy Unit of the University and Hospital of Florence. The distribution according to T and N staging with polytomography was compared to patients (106 out of 217) who had CT scans done at presentation. T1 cases were less frequent (6.6% vs 27%) in the CT-staged series, whereas T3 showed a higher incidence (30.2% vs 12.6%). The advantages of CT over conventional tomography were quantitated in a subset of 97 patients who underwent both staging procedures. Site-by-site, CT displayed a higher percentage of involvement than polytomography: parapharyngeal spread 18% vs 2%, oropharynx 16% vs 8%, choanae and nasal cavities 28% vs 13%, ethmoid and maxillary sinus 29% vs 13%. Information provided by CT caused a T-stage conversion in 23 out of 97 cases (23%): 4 out of 11 T1, 16 out of 44 T2, 3 out of 16 T3.

Humans↗

Value of tumor size in predicting survival from renal cell carcinoma among tumors, nodes and metastases stage 1 and stage 2 patients.

Results in the literature are inconsistent regarding the value of tumor size in predicting survival from renal cell carcinoma, and its use as a staging variable in the current tumors, nodes and metastases system has been questioned. In this study tumor size had no prognostic significance in Kaplan-Meier or Cox regression models examining survival differences between 93 patients with stage T1N0M0 and T2N0M0 renal cell carcinoma dichotomized by tumor size cutoffs at 2.5, 5, 7.5 or 10 cm. In multivariate Cox regression models for 122 patients with stage T1NallMall or T2MallMall renal cell carcinoma, metastatic disease was the strongest predictor of survival, and patients with smaller tumors had significantly longer survival than those with larger tumors at all cutoffs except 2.5 cm., for which differences were insignificant. A 5 cm. cutoff maximized the value of tumor size in predicting survival. If tumor size is to remain the variable by which tumors, nodes and metastases stages T1 and T2 disease are differentiated, a 5 cm. cutoff should replace the current 2.5 cm. definition.

Carcinoma, Renal Cell↗