The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic ...phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy.
In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98).
With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval CI, 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P =.27). There was no statistically significant difference in OS (P =.19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group.
Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.
Tumor risk stratification during diagnosis is paramount for children with medulloblastomas, primarily because very young patients (<3 years) suffer cognitive deficits from radio- and chemotherapy ...sequelae. Thus, distinguishing tumors that are biologically more aggressive is essential for medulloblastoma management to maximize the delay in radiation treatment without adversely affecting survival outcome. In this context, current strategies for risk assessment, which are based on clinical parameters, remain unsatisfactory.
Array-based comparative genomic hybridization (aCGH) was used to identify chromosomal copy number abnormalities in a cohort of 49 medulloblastoma tumors. Based on the karyotypes generated from aCGH analysis, each tumor was scored for copy number abnormalities, and the log-rank test was used to evaluate whether any cytogenetic events were associated with survival.
A single copy gain of 1q was shown to be a negative prognostic marker for survival in medulloblastomas with high statistical significance (P < 0.0001, log-rank test).
A gain of 1q provides a potential means of predicting overall survival in medulloblastoma.
To evaluate toxicity, survival, and recurrence-free interval in women with loco-regionally advanced endometrial carcinoma treated with postoperative whole abdominal radiation therapy.
Whole abdominal ...irradiation with pelvic plus or minus para-aortic boost was initiated within 8 weeks of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and selective pelvic and para-aortic node sampling in eligible, consenting patients.
Of 180 evaluable patients entered on the study with surgically staged III and IV endometrial carcinoma maximally debulked to less than 2 cm, 77 had typical endometrial adenocarcinoma and 103 had high-risk histology, either papillary serous or clear cell carcinoma. Patients with typical endometrial adenocarcinoma were significantly younger and had significantly fewer poorly differentiated cancers. Proportionally, there were twice as many non-Whites with high-risk histologies as non-Whites with typical endometrial adenocarcinoma. Forty-five percent of patients with typical endometrial adenocarcinomas had positive pelvic nodes compared to 51% of those with high-risk histologies. Both histologic groups had similar distribution for performance status, para-aortic node positivity, site and extent of disease, and International Federation of Gynecology and Obstetrics (FIGO) stage. The frequency of severe or life-threatening adverse effects among 174 patients evaluable for radiation toxicity included 12.6% with bone marrow depression, 15% GI, and 2.2% hepatic toxicity. The recurrence-free survival rates were 29% and 27% (at 3 years) for the typical endometrial adenocarcinoma and high-risk histologies, respectively. The survival rates were 31% and 35%, respectively. No patient with gross residual disease survived.
Whole abdominal irradiation in maximally resected advanced endometrial carcinoma has tolerable toxicity, and it is suggested that the outcome may be improved by this adjunctive treatment in patients with completely resected disease.
Gynecologic Oncology Group Protocol 52, a randomized trial of cisplatin and cyclophosphamide with or without doxorubicin in "optimal" Stage III epithelial ovarian cancer, failed to demonstrate a ...significant difference in the outcome in 349 evaluable patients. Additional review of the records was carried out to determine the influence of cytoreductive surgery on survival. Since eligibility for the study was the presence of residual cancer of 1 cm or less, the influence of cytoreductive surgery could be evaluated by comparing outcome in patients presenting with large-volume extrapelvic disease, but who were cytoreduced to small-volume disease. Factors evaluated were age, cell type, grade, size, and location of disease at exploration, size, and location of residual disease after cytoreduction, number of residual nodules, ascites, type of surgery, blood loss, and hospital days. Univariate analysis revealed that age, size of residual disease, mucinous or clear cell histologic type, histologic grade, and number of residual lesions were significant prognostic factors. By univariate analysis patients found to have extrapelvic disease of 1 cm or less had a better recurrence-free interval and survival than those patients with large-volume disease who were cytoreduced to disease of 1 cm or less. Multivariate analysis revealed that older age, histologic grades 2 and 3, and 20 or more residual lesions were unfavorable. The volume of initial extrapelvic disease remained significant when gross disease was present in the omentum and in other extrapelvic sites. This study failed to prove the hypothesis that initial cytoreductive surgery would allow a patient presenting with large-volume ovarian cancer to have the same chance for survival as a patient found to have small-volume disease. Factors other than cytoreductive surgery are important in predicting survival.
Introduction: Non‐dystrophic myotonia (NDM) is characterized by myotonia without muscle wasting. A standardized quantitative myotonia assessment (QMA) is important for clinical trials. Methods: ...Myotonia was assessed in 91 individuals enrolled in a natural history study using a commercially available computerized handgrip myometer and automated software. Average peak force and 90% to 5% relaxation times were compared with historical normal controls studied with identical methods. Results: Thirty subjects had chloride channel mutations, 31 had sodium channel mutations, 6 had DM2 mutations, and 24 had no identified mutation. Chloride channel mutations were associated with prolonged first handgrip relaxation times and warm‐up on subsequent handgrips. Sodium channel mutations were associated with prolonged first handgrip relaxation times and paradoxical myotonia or warm‐up, depending on underlying mutations. DM2 subjects had normal relaxation times but decreased peak force. Sample size estimates are provided for clinical trial planning. Conclusion: QMA is an automated, non‐invasive technique for evaluating myotonia in NDM. Muscle Nerve 46: 482–489, 2012
A non-randomized comparison of outcome in women undergoing second-look laparotomy (SLL) or clinical follow-up, after receiving six cycles of combination chemotherapy with paclitaxel plus either ...cisplatin or carboplatin, for optimally resected stage III ovarian cancer.
Prior to chemotherapy randomization, patients chose whether or not to undergo SLL; this was a stratification factor to insure balance of treatment assignment. Any subsequent therapy was physician-directed. Explanatory analysis replaced intent-to-treat because of a higher likelihood of detecting SLL effect in the presence of noncompliance.
There were 393 patients (median age: 54) who Elected SLL and 399 (median age: 59) who Elected No SLL. The former group was more likely to have gross residual disease at initial surgery than the latter group (69% versus 60%, respectively). In the Elected SLL group, 59 (15%) patients subsequently refused surgery, in nine (2%) surgery was contraindicated, and 31 (8%) relapsed or died prior to the procedure. Cancer was found in 46% of 294 (75%) patients undergoing SLL. Since early failures (prior to SLL) do not address benefit, such patients (SLL: 32; No SLL: 33), defined as progression-free survival (PFS) < 6 months, were excluded from analysis. The adjusted relative risk of progression is 0.89 (95% confidence interval: 0.75, 1.07); the difference in median PFS is 1.0 month (SLL: 23.9 months; No SLL: 22.9 months). The survival rate curves are superimposable.
In the context of a non-randomized comparison, the performance of a SLL was not associated with longer survival.
Although it was observed that inhibition of the antiapoptotic protein survivin expression in lung cancer cells induces apoptosis, the expression and role of survivin variants (survivin-2B and ...survivin-ΔEx3) in lung cancer have not yet been characterized. We analyzed 24 non-small-cell lung cancer (NSCLC) samples by semi-quantitative RT-PCR. Surprisingly, our results revealed that high-level expression of survivin-2B is significantly associated with the patient category of “no relapse and alive” (
p-value
<
0.0001). In contrast, high-level expression of survivin-ΔEx3 is highly associated with the patient category of “relapse and dead” (
p-value
<
0.0001). Consistent with this observation, exogenous expression of survivin-2B in A549 lung cancer cells inhibited cell growth, disrupted the mitochondria potential, and induced apoptotic cell death, while expression of survivin-ΔEx3 protected the mitochondria potential and facilitated cell survival. These findings provide evidence that survivin-2B and survivin-ΔEx3 play opposite roles in disease relapse and NSCLC cell survival, which is likely through the differential modulation of mitochondrial potential. Thus, controlling the differential expression of survivin-2B and survivin-ΔEx3 may represent novel approaches for cancer therapeutics in NSCLC.
Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. ...Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients.
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