scholarly journals Advancing Cancer Diagnostics with Artificial Intelligence (AI) and Biomedical Vibrational Spectroscopy for Identifying Chemical Changes Associated with Breast Cancer

2021 ◽  
pp. 680-725
Author(s):  
Elena Locci ◽  
Silvia Raymond

The CARTITUDE-1 study is a stage 1B / II clinical trial. The trial targeted B-cell maturation antigen by targeting CAR-T cell therapy in patients with multiple myeloma who had received at least three previous lines of treatment with standard drugs, including proteasome inhibitors, immunosuppressive drugs, and CD38 antibodies. Cilta-cel is made from the patient's own T cells, which is genetically engineered and is given as a single injection. The overall response rate to treatment was 97%, while the complete response rate and progression-free survival rate were 67% and 77%, respectively. The overall survival rate was 89%. Updates to this study were recently presented at the annual meeting of the American Clinical Oncology Association after our paper was accepted for publication in The Lancet. Our ASCO presentation showed a deeper response for patients receiving this treatment. These results are very impressive for patients with myeloma who have already undergone many treatment lines for their disease. It will be important to better understand the clinical features of patients who have experienced long-term recovery from this treatment and the mechanisms by which patients’ relapse. While it is not possible to formally conduct two separate single-arm studies on the idea of cells and cilia, the rate of dramatic response and progression-free survival of eyelash-treated patients is very interesting. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.


2005 ◽  
Vol 23 (36) ◽  
pp. 9198-9207 ◽  
Author(s):  
Paolo G. Gobbi ◽  
Alessandro Levis ◽  
Teodoro Chisesi ◽  
Chiara Broglia ◽  
Umberto Vitolo ◽  
...  

Purpose In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to ≤ two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program). Patients and Methods Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively. Results The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens). Corresponding 5-year overall survival rates were 90%, 82%, and 89% for ABVD, Stanford V, and MOPPEBVCAD, respectively. Stanford V was more myelotoxic than ABVD but less myelotoxic than MOPPEBVCAD, which had larger reductions in the prescribed drug doses. Conclusion When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 407-407 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  

Abstract BACKGROUND: In newly diagnosed patients, the addition of thalidomide or bortezomib (Velcade™) to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter, open-label, non randomized, phase I/II trial, the safety/efficacy profile of the 4 drug combination, bortezomib (Velcade™), melphalan, prednisone, and thalidomide (VMPT) was evaluated in patients with relapsed/refractory myeloma. METHODS: Bortezomib was administered by IV bolus on days 1, 4, 15, 22 at three dose levels: in the first cohort (10 patients) at 1.0 mg/m2; in the second cohort (10 patients) at 1.3 mg/m2and in the third cohort (10 patients) at 1.6 mg/m2. Oral melphalan was administered at 6 mg/m2 on days 1–5, oral prednisone at 60 mg/m2 on days 1–5. Thalidomide was delivered at 50 mg on days 1–35. Each course was repeated every 35 days for a total of 6 courses. RESULTS: Thirty patients, median age 66 years (range 38–79), with relapsed or refractory myeloma were enrolled. Fourteen patients received VMPT as second line of therapy, 16 as third line. Twenty patients received prior autologous transplant, 10 conventional chemotherapy and 9 thalidomide-based regimens. After a median of 6 courses, 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good partial response (VGPR). Among patients who received VMPT as second line treatment, the PR rate was 79%, and the immunofixation negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 non-hematological adverse events included: infections (5 patients), fatigue (1), vasculitis (1) and peripheral neuropathy (2); no grade 4 toxicities were recorded. CONCLUSIONS: Initial results showed that VMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. The incidence of neurotoxicities was unexpectedly low.


2013 ◽  
Vol 23 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Tamar Safra ◽  
Tara Berman ◽  
Adelya Yachnin ◽  
Ilan Bruchim ◽  
Mihai Meirovitz ◽  
...  

ObjectivesThe purpose of this study was to assess the clinical activity and toxicity of weekly topotecan in a large cohort of epithelial ovarian (EOC), primary peritoneal (PPC), and tubal cancer patients.MethodsRecords of patients with recurrent EOC, PPC, and tubal cancer who were treated with weekly topotecan (4.0 mg/m2 on days 1, 8, and 15 on a 28-day cycle) after failure of more than 1 prior regimen were retrospectively reviewed in 8 centers in Israel.ResultsTwo hundred four patients were evaluated for efficacy and toxicity. Median age was 62 years (range, 27–89 years); 121 (59.3%) were platinum sensitive. Patients were exposed to a median of 2 previous lines (range, 1–9), and 48.5% received only 1 prior chemotherapy regimen. Median follow-up was 15.5 months (range, 2.5–112 months). Overall response rate was 26.5%, of which 11 patients (5.4%) had complete response, and 43 patients (21.1%) had partial response. Clinical benefit rate (complete response + partial response + stable disease) was 65.7%. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.5–4.5 months). There was no significant difference between platinum-sensitive and platinum-resistant patients regarding response rate or progression-free survival. Median overall survival from disease diagnosis was 45.0 months (95% CI, 40.04–49.6 months) and 16.0 months (95% CI, 12.3–19.7 months) from initiation of topotecan therapy. Overall survival was significantly different between patients with platinum-sensitive and platinum-resistant disease (19.9 vs 10.8 months, respectively, P = 0.003; 95% CI, 8.1–16.3 months). Multivariate analysis showed that only platinum sensitivity and topotecan line were associated with overall survival. Weekly topotecan was well tolerated—with only 16.7% of patients experiencing grade 3 to 4 hematologic toxicities. There were no other grade 4 toxicities, and only 6.9% grade 3 toxicities.ConclusionsIn this large cohort of recurrent EOC, PPC, and tubal cancer, weekly topotecan was well tolerated with good clinical benefit rate, comparable to previous studies.


2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.


Author(s):  
Cristina Gasparetto ◽  
Gary J. Schiller ◽  
Sascha A. Tuchman ◽  
Natalie S. Callander ◽  
Muhamed Baljevic ◽  
...  

Abstract Background Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM). Methods The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib. Results Thirty-two patients, median prior therapies 4 (range, 1–8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months. Conclusions Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2010-2010
Author(s):  
Eric Yamga ◽  
Richard Leblanc ◽  
Jean-Samuel Boudreault

Abstract Background: Multiple myeloma (MM) is the second most common hematologic cancer. The management of this disease consists of induction therapy followed by autologous hematopoietic stem cell transplantation (HCT). There is no standard of care as for the best induction regime. Recently, the first phase III study (Moreau P and all.) comparing two chemotherapy triplets in transplant-eligible patients, suggested a superiority of VTD over VCD. Although VTD was associated with better treatment response rates, the survival data remains to be seen. We wanted to retrospectively compare 3 Bortezomib-based therapies using response rates (RR), progression-free survival (PFS) and overall survival (OS). Bortezomib-Cyclophosphamide-Dexamethasone (CyBorD) remains the standard in Canada. Method: A total of 75 patients induced between 2010 and 2016 were analyzed. Their charts were reviewed and the data was retrospectively collected. Three distinct treatment groups were included : Vd (19), CyBorD (39) and VTD (17).The main outcome was treatment response rate, 2-year progression-free survival rate (PFS) and 2-year overall survival rate (OS). The secondary outcome was median PFS. Results: Patient characteristics are presented below (table 1). The difference between the treatment response rates were non-statistically significant but demonstrated a favorable trend towards VTD as the VGPR rate was 58.8%, 65% and 88.1% respectively in the Vd, CyBoRD and VTD groups (table 2 and 3). Median progression-free survival was significantly longer in the group that received VTD than in the group that received CyBord (3.58 years vs. 2,80 years; P = 0.03). The 2-year overall survival rate was 88,9%, 96,3% et 93,3% respectively in the 3 groups (table 4). Conclusion: The data from this retrospective study supports the superiority of the VTD induction regimen compared with CyBorD and Vd in terms of response rate and progression-free survival. However, there is no major difference in overall survival over the time period observed. Disclosures Leblanc: Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees. Boudreault:Celgen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16068-16068
Author(s):  
S. Takeuchi ◽  
H. Tsubamoto ◽  
S. Adachi ◽  
K. Ito ◽  
Y. Itani ◽  
...  

16068 Background: For optimal debulked mullerian cancer (MC), the Intraperitoneal (IP) therapy has become the effective modality of chemotherapy to obtain better prognosis. We have reported KCOG9811study: IP CDDP + Paclitaxel (PTX) intravenous (IV) 2 cycles followed by 3 cycles of usual PTX-Carboplatin (abstr.1970, ASCO2002). And we have also reported the feasibility study and satisfactory response rate of the weekly IP-PTX with IV Carboplatin therapy (IP-PIVC, abstr. 5120, ASCO2005). Objectives: We have conducted two types of IP therapy for optimal debulked MC to improve the progression free survival (PFS) and overall survival (OS). Here are the prognosis and recurrent fashion after these IP therapies. Methods: Twenty patients (pts) with optimal debulked ovarian cancer were enrolled for KCOG9811, and eleven pts with optimal debulked MC newly/recurrent diagnosed disease were enrolled for IP-PIVC. The regimen of each therapy consisted of as follows: KCOG9811:50mg/ m2 of CDDP was administered via IP port at operation, after 2 weeks (wks) of operation, PTX was administered at a dose of 175mg/ m2IV for 3hrs on day 1, CDDP was administered at 75mg/ m2IP on day 2, every 3wks for 2 cycles, followed by PTX 175mg/ m2 IV and Carboplatin AUC5 IV on day1 every 3wks for 3 cycles. The IP-PIVC therapy consisted of IP-PTX, on days 1, 8, 15 at a dose of 45 mg/m2 (3pts) and 60 mg/m2(8pts). Carboplatin was administered monthly at a dose of AUC 5 on day 1 only. 2–6 cycles were performed. Results: The mean observation time was 72.6 months (m) and 32.6m for KCOG9811 and IP-PIVC, respectively. As for the median PFS was 1308+ days and 678+ days, and the median OS was 2180+ days and 978+ days, respectively. The five years survival rate showed 59.3% on KCOG9811, and the three years survival rate showed 75.8% on IP-PIVC. As for recurrent fashion, liver metastases and proximal lymphnodes metastases, and retroperitoneal metastases were detected. Few cases recurred Intraperitoneal lesion with small ascites Conclusions: There are some differences in the recurrent fashion of IP treatment from that of IV treatment. IP treatment prevented ascitic recurrence. Further improvement of chemotherapy is necessary for liver metastasis and proximal lymphnodes. [Table: see text]


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5547-5547
Author(s):  
Liu Xiaoli ◽  
Li Ding ◽  
Na Xu ◽  
Bintao Huang ◽  
Xuan Zhou ◽  
...  

Abstract Objective Whetherinterferon alpha (IFN-α) has special therapeutic effect formyeloproliferative neoplasm (MPN) patients with JAK2V617F mutations was not widely confirmed. Our purpose was to evaluate the therapeutic effect of interferon alpha (IFN-α) in MPN patients with JAK2V617F mutations. Methods A total of 99 advanced MPN patients (including 68 polycythemia vera (PV) patients with 34 JAK2V617F mutations and 68 essential thrombocytosis (ET) with JAK2V617F mutations) patients) were enrolled to the study during 2007 to 2013 with informed consent, then they were divided into two groups: the IFN-α group (patients received a standard dose of IFN-α with (30-50)ug/d ) and the Hydroxyurea (HU) group (patients received a a dose of (0.25-0.5)g/d for HU). The progression-free survival rate were analyzed for a median of 32.0 (6.0 to 60.0) months follow-up period. Results The overall response rate between IFN-α and Hydroxyurea therapy groups of essential thrombocytosis (ET) patients with JAK2V617F mutations had no significant difference (88.2% vs 85.0%, P>0.05), but the 5-year progression-free survival rate of two groups showed significant difference (88.2% vs 55.0%, P<0.05). The overall response rate (78.6% vs 82.4% ) and 5-year progression-free survival rate (57.1% vs 58.8%) between IFN-α and Hydroxyurea therapy groups of ET patients without JAK2V617F mutations had no significant difference (P>0.05). The overall response rate between IFN-α and Hydroxyurea therapy groups of polycythemia vera (PV) patients with JAK2V617F mutations had no significant difference (80.0% vs 75%, P>0.05), but the 5-year progression-free survival rate of IFN-α and Hydroxyurea therapy groups showed significant difference (86.7% vs 50.0%, P<0.05). After the treatment of IFN-α and HU for six months, the ratio of Interferon-treated patients need to continue phlebotomy was significantly lower than hydroxyurea therapy group (8.3% vs 58.3%, P<0.05). The thromboembolic events,splenomegaly, bone marrow fibrosis of interferon treatment group were lower than hydroxyurea treatment group showed significant difference (P<0.05). The adverse reactions of IFN-α was moderate, most of the patients in this study could tolerate the therapy. The major side effect of hydroxyurea was hematologic adverse reactions (Grade 1-2) with mainly reduce of white blood cells and thrombocytopenia, which showed difference between IFN-α and hydroxyurea (P<0.05). Conclusions IFN-α may improve the prognosis of ET and PV patients with JAK2V617F mutations. Moreover, patients with PV and JAK2V617F mutations may be benefit for the treatment of IFN-α and could be recommended for an effective choice. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2767-2772 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  

AbstractIn multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.


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