PML-RARα isoform at diagnosis is associated with disease-free survival (DFS) in patients enrolled in the intergroup trial (C-9710) for treatment of acute promyelocytic leukemia (APL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6504-6504 ◽  
Author(s):  
W. Stock ◽  
B. Moser ◽  
D. A. Sher ◽  
E. Schachter-Tokarz ◽  
M. Myers ◽  
...  
Keyword(s):  
Platelet Count ◽  
Fusion Gene ◽  
Randomized Study ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Transcript Levels ◽  
Future Risk ◽  
Pre Treatment

6504 Background: Refinement of prognostic groups using molecular genetic features of the disease may facilitate the design of future risk-adapted trials for APL. Previous analyses of the prognostic value of PML-RARα transcript levels and isoform type have generated conflicting results. We sought to determine the clinical significance of measuring PML-RARα transcript level at the time of diagnosis using real-time quantitative RT-PCR (RQ-PCR) of the long (L) and short (S) isoforms of the fusion gene. Methods: PML-RARα transcript levels were measured in pretreatment bone marrow (BM) and/or paired blood (B) samples of 139 patients (pts) with newly diagnosed APL registered to C-9710, the intergroup phase III randomized study of concurrent tretinoin and chemotherapy with or without arsenic trioxide as initial consolidation therapy. Transcript levels were expressed as the normalized quotient (NQ) of PML-RARα/ABL or PML-RARα/GAPDH. Correlations between pre-treatment NQ values and other pre-treatment characteristics including age, presenting WBC and platelet count, and L or S isoform were explored. Results: Pre-treatment NQ values using ABL vs. GAPDH showed significant correlation (p < 0.0001). Pre-treatment transcript levels in B and BM for 57 pts with S-form were significantly higher than 82 L-form patients (p = 0.02) when NQ was determined using GAPDH as the control gene (but not with ABL). With a median follow-up of 24.3 months for all patients, there have been 19 events. Median DFS for either isoform has not been reached, however, DFS was significantly shorter for patients with S-isoform compared to those with L-isoform (p = 0.017) with an estimated hazard ratio of 3.28. Using a multivariate proportional hazard model, no other significant relationships were found between DFS and NQ level at diagnosis, age, presenting WBC or platelet count. Conclusions: The S-isoform of the PML-RARa fusion gene was associated with shorter DFS in a subset of patients entered onto C-9710. If confirmed in a larger cohort of C-9710 pts, presence of the S-isoform should be considered as a high-risk feature in the design of future risk-adapted treatment strategies for APL. No significant financial relationships to disclose.

scholarly journals Three-year outcomes of the randomized phase III SEIPLUS trial of extensive intraoperative peritoneal lavage for locally advanced gastric cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Guo ◽  
Aman Xu ◽  
Xiaowei Sun ◽  
Xuhui Zhao ◽  
Yabin Xia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Peritoneal Lavage ◽  
Randomized Study ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Phase Iii ◽  
Free Survival ◽  
Locally Advanced Gastric Cancer

AbstractWhether extensive intraoperative peritoneal lavage (EIPL) after gastrectomy is beneficial to patients with locally advanced gastric cancer (AGC) is not clear. This phase 3, multicenter, parallel-group, prospective randomized study (NCT02745509) recruits patients between April 2016 and November 2017. Eligible patients who had been histologically proven AGC with T3/4NxM0 stage are randomly assigned (1:1) to either surgery alone or surgery plus EIPL. The results of the two groups are analyzed in the intent-to-treat population. A total of 662 patients with AGC (329 patients in the surgery alone group, and 333 in the surgery plus EIPL group) are included in the study. The primary endpoint is 3-year overall survival (OS). The secondary endpoints include 3-year disease free survival (DFS), 3-year peritoneal recurrence-free survival (reported in this manuscript) and 30-day postoperative complication and mortality (previously reported). The trial meets pre-specified endpoints. Estimated 3-year OS rates are 68.5% in the surgery alone group and 70.6% in the surgery plus EIPL group (log-rank p = 0.77). 3-year DFS rates are 61.2% in the surgery alone group and 66.0% in the surgery plus EIPL group (log-rank p = 0.24). The pattern of disease recurrence is similar in the two groups. In conclusion, EIPL does not improve the 3-year survival rate in AGC patients.

scholarly journals Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study

2019 ◽  
Vol 37 (25) ◽  
pp. 2246-2256 ◽  
Author(s):  
Rob Pieters ◽  
Paola De Lorenzo ◽  
Philip Ancliffe ◽  
Luis Alberto Aversa ◽  
Benoit Brethon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Study Groups ◽  
Phase Iii ◽  
Free Survival ◽  
Wbc Count

PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A ( MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 × 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE+MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.

A randomized phase III trial of 1 month versus 1 year adjuvant high-dose interferon alfa-2b in patients with resected high risk melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8505-8505 ◽  
Author(s):  
H. Gogas ◽  
U. Dafni ◽  
D. Bafaloukos ◽  
A. Polyzos ◽  
G. Kokkalis ◽  
...  
Keyword(s):  
Randomized Study ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Induction Phase ◽  
Curative Surgery ◽  
Flat Dose ◽  
Risk Melanoma ◽  
Grade 3 ◽  
Group B

8505 Background: High dose IFNa regimen as reported in E1684 was unique for the incorporation of an induction phase of maximally-tolerated dosages of IV therapy for the initial 4 weeks. This is the only trial that has shown prolongation of overall survival and disease-free survival in comparison to observation. Analysis of the hazard curves for DFS and OS in E1684 reveal early and durable separation of the high-dose and observation arms suggesting that the induction phase may represent a critical component of the high-dose regimen, although this has not been tested prospectively. Methods: We conducted a prospective randomized study of IV induction therapy vs a full year of high-dose IFN with primary endpoints of DFS and OS for stage IIB, IIC and III melanoma patients within 56 days of curative surgery. Patients were randomized to receive IFN alfa-2b 15×106 U/m2 IV × 5/7 days weekly × 4 weeks (arm A) versus the same regimen followed by 10×106 U(flat dose) SC 3 times a week for 48 weeks (arm B). The proposed treatment would be considered at least as good as the conventional treatment, if the relapse rate at 3 years from study entry is at most 15% higher in the former arm (power 85%, one-sided test a=0.05, required sample size: 340). Results: Between 1998 and 2004, 364 patients were enrolled (355 eligible: 178 arm A and 177 arm B). Patients′ and tumor characteristics were well balanced between the two arms. At a median follow up of 51 months (95% CI 46–55), the median DFS is 32 months vs 31 months (p=0.836) and the median OS is 61 months vs 63 months (p=0.444). Eleven patients discontinued treatment in arm A and 54 in arm B. The discontinuation rate is significantly higher in group B (p<0.001), possibly due to the longer duration. Reasons for discontinuation were disease progression (69%) and toxicity (19%). Patients in arm B had more grade 3–4 hematologic, constitutional and neurologic toxicity. Conclusions: There are no significant differences in OS and DFS between the regimen of 1 month and 1 year treatment tested. [Table: see text]

Effect of bexarotene on platelet counts in patients undergoing cancer treatment: An analysis of clinical trials in lung cancer and leukemia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20533-e20533
Author(s):  
D. E. Tsai ◽  
W. Wang ◽  
R. Reshef ◽  
D. Vogl ◽  
E. Stadtmauer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Platelet Count ◽  
Clinical Trial Data ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Two Phase ◽  
Platelet Counts ◽  
Transfusion Independence ◽  
Pre Treatment

e20533 Background: Bexarotene (Bex) is an oral retinoid X receptor agonist with activity against cutaneous T cell lymphoma and currently under investigation for other malignancies. In patients receiving this agent for acute myeloid leukemia (AML), we noted increases in platelet counts. We therefore reviewed the available clinical trial data on Bex and its effects on platelet counts. Methods: We analyzed platelet count data from 3 Bex clinical trials encompassing non-small cell lung cancer (NSCLC) and AML. Results: In two phase III trials of Bex in NSCLC, patients underwent carboplatin + paclitaxel (CarP, n=587) or cisplatin + vinorelbine (CisV, n=613) and were randomized to receive concurrent Bex or placebo. More patients on Bex than on placebo had an increase in platelet count of at least 50 K/uL (55% vs. 27% for CarP, p<0.0001; 81% vs. 66% for CisV, p<0.0001) over pre-treatment baseline. The median increase in platelet count was higher on Bex than on placebo (69 vs 0 K/uL for CarP, p<0.0001; 168 vs. 95 K/uL for CisV, p<0.0001) and was maintained while on treatment. In both NSCLC trials, the median time to platelet increase >50 K/uL on Bex was 22 days. Similar findings were seen in a phase I monotherapy trial in AML where 5/18 (28%) patients achieved platelet transfusion independence with peak platelet counts of 40–91 K/uL. Conclusions: Clinically significant increases in platelet counts were seen in all 3 clinical trials examined. These data suggest that Bex improves platelet counts in patients with a variety of cancer types, both as monotherapy and with concurrent chemotherapy. Its effect on megakaryopoiesis and its potential role as a supportive care measure should be further evaluated. [Table: see text]

Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the phase III KRISTINE study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Miguel Martin ◽  
Kyung Hae Jung ◽  
Chiun-Sheng Huang ◽  
Nadia Harbeck ◽  
...  
Keyword(s):  
Randomized Study ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Her2 Positive ◽  
Free Survival ◽  
Post Surgery ◽  
Grade 3

500 Background: KRISTINE compared neoadjuvant chemotherapy plus dual HER2- blockade (HP) with T-DM1 plus P (T-DM1+P), a targeted regimen that omits standard chemotherapy. T-DM1+P resulted in a lower pathologic complete response (pCR) rate, but a more favorable safety profile. Here we present the final outcomes from KRISTINE. Methods: KRISTINE (NCT02131064) was a randomized study of T-DM1+P versus docetaxel, carboplatin, and H plus P (TCHP). Patients with HER2-positive stage II–III BC received 6 cycles of neoadjuvant T-DM1+P or TCHP q3w. Patients receiving T-DM1+P continued adjuvant T-DM1+P; patients receiving TCHP received adjuvant HP, for 12 cycles in each arm. Patients in the T-DM1+P arm without pCR were encouraged to receive standard adjuvant chemotherapy before adjuvant T-DM1+P. Secondary endpoints, analyzed with descriptive statistics, included event-free survival (EFS; all events pre- and post-surgery), invasive disease-free survival (IDFS; invasive events post-surgery), overall survival and safety. Results: At median follow-up of 37 months, EFS favored TCHP (HR = 2.61 [95% CI: 1.36–4.98]), due to more locoregional progression events in the T-DM1+P arm before surgery (6.7% vs 0; Table). pCR was associated with reduced risk of an IDFS event (HR = 0.24 [95% CI: 0.09– 0.60]) regardless of treatment arm. There were 5 deaths (2.3%) in the TCHP arm and 6 (2.7%) in the T-DM1+P arm. There were more grade ≥3 AEs with TCHP but a higher rate of AEs leading to treatment discontinuation with T-DM1+P. Conclusions: EFS numerically favors TCHP due to locoregional progression events with T-DM1+P prior to surgery. T-DM1+P was associated with fewer grade ≥3 AEs but increased treatment discontinuation. Clinical trial information: NCT02131064. [Table: see text]

Mutations of the TP53 Gene Occur in 13.4% of Acute Myeloid Leukemia and Are Strongly Associated with a Complex Aberrant Karyotype.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1913-1913
Author(s):  
Claudia Schoch ◽  
Frank Dicker ◽  
Hannes Herholz ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
Fusion Gene ◽  
Direct Sequencing ◽  
Mutation Screening ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Normal Karyotype ◽  
Tp53 Gene ◽  
Trisomy 8 ◽  
Tp53 Mutations

Abstract The TP53 gene is the most frequently mutated gene in human tumors identified so far. In a prior study we demonstrated that 78% of AML with complex aberrant karyotype show a mutation of the TP53 gene. The aim of this study was to determine the frequency of TP53 mutations in an unselected cohort of AML and to analyze the relation to cytogenetic and molecular genetic aberrations. In total 149 AML cases were examined by chromosome banding analysis and screened for FLT3-length mutations (FLT3-LM), MLL partial tandem duplication (MLL-PTD), NPM1 mutations, and TP53 mutations. The cohort included cases with t(8;21) (n=10), t(15;17) (n=6), inv(16) (n=4), 11q23/MLL-rearrangement (n=6), trisomy 8 sole (n=13), AML with normal karyotype (n=46), AML with complex aberrant karyotype defined as showing 3 and more clonal abnormalities but no balanced rearrangement leading to a leukemia specific fusion gene (n=26), and AML with other abnormalities (n=38). FLT3-LM were observed in 21, MLL-PTD in 4, and NPM1-Mutations in 26 cases. TP53 mutation screening of exons 3–9 was performed by denaturing high performance liquid chromatography (DHPLC). All mutations detected were verified by direct sequencing. Overall, TP53 mutations were detected in 20 of the 149 cases (13.4%). Within this cohort of TP53 mutated cases, coincidences of FLT3-LM and MLL-PTD, respectively, with TP53 mutation were detected in one case each. A complex aberrant karyotype was present in 17 of 20 cases (85%) with TP53 mutation. The remaining 3 cases with TP53 mutation showed a normal karyotype, a trisomy 8, and t(8;21) as the sole abnormality, respectively. Therefore, we confirmed a high incidence of TP53 mutations in AML with complex aberrant karyotype (17/26, 65.4%). On the other hand TP53 mutations are very rare in AML without a complex aberrant karyotype (3/123, 2.4%). Furthermore, we divided AML with complex aberrant karyotype into two subgroups:AML with “typical” complex aberrant karyotype showing a deletion of at least one of the following regions: 5q31, 7q31, 17p13 (definition according to Schoch et al. GCC, 2005) andAML with “untypical” complex aberrant karyotype comprizing all others. Interestingly, the frequency of TP53 mutations within the “typical” complex aberrant karyotype group was 75% (15/20) while in the “untypical” group it was 33% (2/6) (p=0.138). In conclusion, the overall incidence of TP53 mutations is low in AML. TP53 mutations are highly associated with AML and complex aberrant karyotype and occur very infrequently in all other cytogenetic subgroups (p<0.001). They occur frequently in particular in the subgroup showing a typical pattern of chromosomal deletions (5q, 7q, 17p). TP53 mutations might explain in part the chemoresistance of AML with complex aberrant karyotype. In addition to cytogenetics a rapid diagnostic screening for TP53 mutations could be a valuable tool to identify a subgroup of AML with poor prognosis. This would allow the early assignment of patients to alternative treatment strategies using also options targeting the TP53 pathway.

A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy (RT) with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) (NCIC Clinical Trials Group HN.6).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS5600-TPS5600 ◽  
Author(s):  
John N Waldron ◽  
Wendy Parulekar ◽  
Brian O'Sullivan ◽  
Bingshu E Chen ◽  
Alexander Montenegro ◽  
...  
Keyword(s):  
Randomized Study ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Phase Iii ◽  
Absolute Difference ◽  
Blood Collection ◽  
High Dose ◽  
Eligibility Criteria ◽  
Good Tolerability ◽  
Hpv Status

TPS5600 Background: Standard treatment for locally advanced SCCHN, chemoradiotherapy (CRT), leads to significant acute and long-term morbidity. The demonstration that EGFR antibody (Ab) therapy improves outcome when added to standard RT (Bonner NEJM 2006) and that altered fractionation RT improves outcome compared to standard RT that is of similar magnitude as CRT (Bourhis Lancet 2006), led to the hypothesis that the combination of the two treatment strategies will improve efficacy compared to standard CRT with good tolerability. Methods: HN.6 is a Canadian phase III randomized study comparing standard RT 70Gy/35 over 7 weeks + cisplatin 100mg/m2 d 1, 22, 43 to accelerated RT 70Gy/35 over 6 weeks + panitumumab (anti EGFR Ab)) 9mg/kg 1 week prior to RT, d15, 36. Key eligibility criteria are: SCC of oral cavity, oropharynx, larynx or hypopharynx; TanyN+M0 or T3-4N0M0; adequate organ function and PS. Primary endpoint is progression free survival (PFS). Secondary endpoints include OS, local PFS, regional PFS, distant metastases, swallowing related QOL, functional swallowing outcomes, and economic evaluation (healthcare utilization, health utilities, indirect costs). Tissue and blood collection will allow biomarker evaluation including HPV status. Real time quality review of RT plans with plan data and radiology archiving will allow future analysis of RT parameters relative to toxicity and patterns of failure. Clinical epidemiological data will be prospectively collected and correlated with biomarkers and outcome. Planned sample size is 320 patients over 3.2 years with 3 more years of follow-up and target hazard ratio = 0.7 (absolute difference in control arm 2 year PFS of 12%, power 80%, 2-tail type 1 error 0.05). If superiority is not demonstrated, noninferiority will be tested. One interim analysis is planned. Conduct to Date: Study activation: Dec 2008 and completed accrual in Nov 2011. In Oct 2011, the DSMC recommended trial continuation. Supported by CCSRI grant 021039 and Amgen Inc. ClinicalTrials.gov: NCT00820248.

Sequenced Compared With Simultaneous Anthracycline and Cyclophosphamide in High-Risk Stage I and II Breast Cancer: Final Analysis From INT-0137 (S9313)

2007 ◽  
Vol 25 (6) ◽  
pp. 656-661 ◽  
Author(s):  
Hannah M. Linden ◽  
Charles M. Haskell ◽  
Stephanie J. Green ◽  
C. Kent Osborne ◽  
George W. Sledge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Total Dose ◽  
Early Stage ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Breast Cancer Patients ◽  
Node Negative

Purpose We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A → C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC). Patients and Methods High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously (IV) every 3 weeks for six cycles; or (arm II) in sequence (A → C) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cyles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A → C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy. Results Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor–positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A → C. Grade 4 hematologic toxicity was greater on A → C, but nonhematological grade 4 was similar. Conclusion The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.

Intergroup RTOG 98–11: A phase III randomized study of 5-fluorouracil (5-FU), mitomycin, and radiotherapy versus 5-fluorouracil, cisplatin and radiotherapy in carcinoma of the anal canal

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4009-4009 ◽  
Author(s):  
J. A. Ajani ◽  
K. A. Winter ◽  
L. L. Gunderson ◽  
J. Pedersen ◽  
A. B. Benson ◽  
...  
Keyword(s):  
Statistical Power ◽  
Randomized Study ◽  
Anal Carcinoma ◽  
Disease Free Survival ◽  
Patient Characteristics ◽  
Phase Iii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

4009 Background: An ∼65% 5-year disease-free-survival (DFS) rate from 5-FU/mitomycin/radiation for anal carcinoma needs improvement. Methods: A phase III randomized trial compared 5-FU (1,000mg/m2 days 1–4 and 29–32) plus mitomycin (10mg/m2 days 1 and 29) and radiation (45 to 59 Gy) (Arm A) to 5-FU (1,000mg/m2 days 1–4, 29–32, 57–60 and 85–88) plus cisplatin (75mg/m2 on days 1, 29, 57 and 85) and radiation (45 to 59 Gy; start day=57) (Arm B) in anal carcinoma patients. Stratification included gender, clinical N status and tumor diameter. Primary endpoint was DFS. Statistical power was 80% with two-sided test to detect 10% DFS increase for Arm B. Results: Of 682 patients accrued, 598 were analyzable. Most unanalyzed patients’ data are early. Patient characteristics were balanced. Median age was 55 years, women predominated (69%), 27.5% had >5 cm tumor diameter and 26% had clinically N+ cancer. Preliminary 5-year estimated DFS was 56% for Arm A and 48% for Arm B (p=0.28) and 5-year estimated overall survival was 69% for both arms (p=0.24). Men(p=0.04), clinically N+ cancer (p<0.0001) and tumor diameter >5 cm (p=0.005) independently prognosticated DFS in a multivariate analysis. 5-year colostomy rate was 10% for Arm A and 20% for arm B(p=0.12). Grade 3/4 toxicity rates: non-hematologic=76% for Arm A and 75% for Arm B but hematologic=67% for Arm A and 47% for Arm B(p=0.0004). Conclusions: In Intergroup-98–11, induction 5-FU/cisplatin followed by 5-FU/cisplatin/radiation failed to improve DFS compared to the standard treatment, 5-FU/mitomycin/radiation. Supported by RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115. No significant financial relationships to disclose.

Hepatoblastoma: Review of Pathology, Diagnosis and Modern Treatment Strategies

2020 ◽  
Vol 16 (4) ◽  
pp. 276-291
Author(s):  
Adil A. Abbas ◽  
Alaa M.N. Samkari ◽  
Abeer S. Almehdar
Keyword(s):  
Surgical Techniques ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Staging System ◽  
The United States ◽  
Surgical Approaches ◽  
Beta Hcg ◽  
Individualized Approach ◽  
Pre Treatment ◽  
Consensus Classification

Hepatoblastoma (HB) is the most common primary malignant hepatic tumor of childhood and, occurring predominantly in the first two years of life. Approximately 100 cases are diagnosed every year in the United States of America. The management of HB has changed markedly over the last three decades. Alfa feto protein (AFP) and beta human chorionic gonadotrophin (beta HCG) are the main tumor markers and are markers for diagnosis and follow up. International collaborative efforts have led to the implementation of the Pre - Treatment Extent of the Disease PRETEXT staging system consensus classification to assess upfront resectability. Complete surgical resection plays a key role in successful management. Overall, outcomes have greatly improved over the past decades mainly because of advances in chemotherapy (CTR) agents and administration protocols, newer surgical approaches and liver transplantation (LT). Targeted medications towards the newly discovered &#946;-catenin and Wnt genetic pathways in tumor cells may soon become an option for treatment. The current disease free survival (DFS) rates are approaching 85%. For the 25% of patients with metastasis at presentation, the overall survival (OS) remains poor. A more individualized approach to treating the heterogeneous spectrum of HB may become the basis of successful treatment in complex cases. Newer medications and surgical techniques are being exploited. Here we present a comprehensive review of the recent advances in the management of HB. A wide literature search was made using internet search engines such as PubMed and Google scholar. More than 100 articles were reviewed and the information extrapolated was arranged to produce this review.

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