CT Regimen Research Articles

Long-term survival after neoadjuvant therapy for triple-negative breast cancer under different treatment regimens: a systematic review and network meta-analysis

BackgroundTriple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC.MethodsPubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS.ResultsWe conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%).ConclusionsThis NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR.

Experience in the treatment of Hodgkin’s lymphoma associated with HIV

Background. Among malignant neoplasms in HIV-infected patients lymphomas occupy a special place due to the high incidence, course characteristics, and difficulties that arise during diagnosis and during antitumor drug therapy. Hodgkin’s lymphoma (HL) is not an AIDS indicating disease, but the risk of its development in people infected with HIV is 5–25 times higher than the incidence of HL in the general population. Prior to the use of antiretroviral therapy, the results of standard chemotherapy in HIV-infected patients with HL were significantly worse than in HIV-negative patients. One of the main requirements for drug treatment of this group of patients is the simultaneous use of antiretroviral therapy and chemotherapy. The aim was to study the clinical characteristics and results of treatment of HL in the presence of HIV infection. Materials and methods. The analysis included 24 HL patients with HIV infection who received treatment in the Department of Radiation and Drug Therapy of Hemoblastoses of the MRRC in the period from 2018 to 2022. Treatment program selection was in accordance with the HL treatment protocol developed at our Center. Patients received 4–6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or 6 cycles of BEACORP (bleomycin, vepesid, doxorubicin, cyclophosphamide, vincristine, dacarbazine, prednisolone) chemotherapy according to the stage of the disease and the risk factors generally accepted for patients with HL. The response to therapy was assessed according to the Lugano-2014 criteria. Descriptive statistics methods were used. Overall survival and progression-free survival were analyzed using the Kaplan-Meier method. Results. HL occurring against the background of HIV is most often represented by a widespread nodal and extranodal lesion, accompanied by symptoms of intoxication (B-symptoms). The use of standard CT regimens as induction therapy for HL in the presence of HIV makes it possible to obtain satisfactory immediate and long-term results of treatment. In our study complete and partial responses were achieved in 94.1 %. With a median follow-up of 12 months survival without progression and overall survival were 75 % and 100 % respectively.

JUSTIFIKASI PROTOKOL COMPUTED TOMOGRAPHY CARDIAC PROSPECTIVE DAN RETROSPECTIVE DITINJAU DARI ANALISIS KUALITAS CITRA DAN ESTIMASI DOSIS RADIASI

Cardiac CT is an imaging technique that detects the condition of the coronary arteries. EKG-triggered techniques are used to improve the resolution of coronary artery images and minimize artifacts caused by cardiac motion. Retrospective cardiac computed tomography remains the first choice for maximum image quality, especially in relative contraindications such as arrhythmias and high heart rates during the cardiac cycle. The prospective technique can significantly reduce the radiation dose compared with the retrospective technique. This study aimed to see the effectiveness of this prospective technique in terms of radiation dose and image quality. The effective dose analysis method is with indoseCT software and calculated with a formula from CTDIvol and DLP. Image quality was assessed by calculating the SNR by comparing prospective and retrospective techniques. The study results regarding image quality show that the retrospective method has an SNR value of 44, and the SNR value of the prospective method is 35. Dose estimation by indoseCT software obtained results. Retrospective techniques yield the following results: The effective dose is 24.09 mSv, and the prospective technique provides an effective dose of 12.54 mSv. Using the prospective technique shows that the dose can be reduced by 47.94% compared with the retrospective technique. The estimated dose was manually calculated based on CTDIvol and DLP, resulting in an effective dose of 33.5 mSv with the retrospective technique and an effective dose of 11.95 mSv with the prospective technique. Using the prospective technique shows that the dose can be reduced by 64.32% compared with the retrospective technique. The rationale for choosing a potential cardiac CT regimen must be careful and precise, as it may not apply to all patients. Use recommendations apply only to patients with low, stable heart rates and less than five bpm variability. Keywords: CT Cardiac, effective dose, Retrospective ECG-Gating, Prospective ECG-Gating.

Management of Early-onset Metastatic Colorectal Cancer (ERMIONE): A single institution analysis.

3593 Background: Despite rising incidence and mortality reported worldwide for CRC diagnosed in pts aged < 50 yrs, currently early onset metastatic CRC (EOmCRC) are treated as their older counterparts. We aimed to investigate how this specific subgroup is treated in real world. Methods: This an observational, retrospective, monocentric study aiming to describe features, management and prognosis of EOmCRC. Pts with EOmCRC treated at our Institution between Apr2002 and Dec2022 were included. Applying a descriptive method, counts and percentages were reported for categorical variables, while median and range for continuous variables. PFS and OS were estimated with the Kaplan-Meier method. A multivariate Cox regression analysis was performed. Results: 172 pts were included, of those 60.5% were female and 66% had an ECOG PS of 0. Median age at diagnosis was 43 yrs (range 12-49 yrs). Metastatic disease was mainly synchronous (72.1%), while only 12.2% and 15.7% were stage II and III at diagnosis and developed metachronous metastases. Primary tumor was left-sided in 70.1%. Metastatic site was most frequently liver (67.4%), followed by peritoneum (41.3%), lungs (33.7%), ovary (23.2%) and bones (9.9%). Disease was mostly widespread, while only 30.2% had a single metastatic site. MMR status was available for 87.2% of pts, being proficient in 90% and deficient in 10%. RAS/BRAF status was available for 95.3% of cases, of those 47.5% was RAS/BRAF wt, 48.2% was RAS mt and 4.3% was BRAF mt. 42.4% of cases had a family history positive for cancer. Germline pathogenic or likely pathogenic variants were identified in 6.4% of cases, of those 63.6% involved MMR genes and 18.2% involved HRD genes. Median number of lines of treatment received was 2 (range 1–6). Most frequent first line regimen was a doublet CT (69.8%), followed by a triplet CT (23.8%) and immunotherapy (4.1%), CT regimens were associated to bevacizumab in 45.3% of cases and to antiEGFRs in 29.1% of cases. Throughout the whole continuum of care 8.7% of pts received immunotherapy and 21.5% received treatment within a clinical trial. 70.3% of pts received surgery and/or local ablative treatments (LATs) with radical intent (52.9% surgery, 12.2 both, 4.6% LATs). At a median FU of 38.6 m, mPFS for first line was 13.5 m (95%CI 12.1-15.0 m) and mOS was 41.5 m (95%CI 33.9 - 44.1 m). Median OS was significantly longer for pts who received surgery and/or LATs compared to those who did not (43.4 vs 23.6 m, p < .0001). At multivariate analysis, besides surgery and/or LATs (p= .0007), BRAF status (p= .0165) and ECOG PS (p= .0209) independently correlated with OS. Conclusions: We confirmed that EOmCRC is more frequently diagnosed as synchronous disease, due to delayed diagnosis. Despite the small population and the retrospective nature, we showed that combining surgery and/or LATs to systemic therapy is associated with increased OS in EOmCRC. These evidence warrant further validation in prospective setting.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Enteropathy associated T-cell lymphoma (EATL) is a rare peripheral T-cell lymphoma (PTCL) associated with celiac disease that has a poor prognosis. Treatment of EATL is challenging due to the lack of clinical trials. In PTCL, the preferred chemotherapeutic regimen is cyclophosphamide, doxorubicine, vincristine and prednisone (CHOP), either with or without etoposide (CHOEP) followed by consolidative autologous stem cell transplantation (ASCT). This nationwide Dutch study describes the incidence, treatment and outcome of all reported EATL cases. Methods: All patients diagnosed with EATL between 1989 and 2020 were identified in the Netherlands Cancer Registry with survival follow-up through February 1, 2022, thereby excluding post-mortem diagnoses. Baseline characteristics, treatment modality and survival outcomes were collected. Patients were categorized into three periods (1989–1999, 2000–2010, 2011–2020) and in limited (I/II) or advanced (III/IV) stage disease. For patients diagnosed as of 2014, detailed information on treatment regimens was available. Overall survival (OS) was defined as the time from diagnosis to all-cause-death. Multivariable analysis of OS was performed using Cox regression. Results: We included 338 patients (median age 67 years [range 37–90 years], 57% male) in our study. Limited stage disease was more common than advanced stage (51% versus 38%, 11% undetermined). Treatment consisted of surgery (18%), chemotherapy (CT; 33%), CT followed by ASCT (3%), surgery and CT (19%), surgery and CT followed by ASCT (3%), surgery and RT (1%) or no treatment (23%). Between 2014 and 2020, the most commonly used CT regimens were CHOP (54% in limited stage and 66% in advanced stage disease) and CHOEP (32% in all stages). Over time, the use of CT increased from 22% to 46%, whereas resection only and resection combined with CT became uncommon (decrease from 33% to 7%, and 23% to 5% respectively; Figure 1). Two-year OS improved from 19% in 1989–1999 to 26% in 2011–2020. The 6-month, 2-year and 5-year OS for limited stage were 51%, 24% and 15% (median OS 6.3 months) and for advanced stage 44%, 16% and 7% (median OS 5.1 months), respectively (Figure 2). In multivariable analysis, surgery only (hazard ratio [HR] 1.97; 95% confidence interval [CI] 1.41–2.74), no therapy (HR 3.66; 95% CI: 1.72–3.76) and advanced stage disease (HR 1.31; 95% CI: 1.02–1.70) were independent predictors of poor prognosis, whereas ASCT (HR 0.38; 95% CI: 0.17–0.81) was associated with improved OS. Keyword: aggressive T-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Abstract P1-11-17: The real-world outcome of human epidermal growth factor type-2 positive breast cancer patients receiving neoadjuvant therapy with or without pertuzumab

Abstract Background Standard treatment in early HER2 positive BC involves the use of neoadjuvant chemotherapy (NACT) with Trastuzumab (T) plus Pertuzumab (P). Dual blockade increases pathological complete response (pCR) and improves disease free survival (DFS). However, Chilean public health system does not include P use in the NACT schedule, while private insurers only provide partial coverage. Here, we aim to compare pCR, Distant DFS (DDFS) and site of recurrence in HER2 positive BC patients treated in the neoadjuvant setting with the use of T with or without P, in the largest BC Chilean registry. Methods We conducted a retrospective population-cohort study involving females with stage I-III HER2 positive BC treated with NACT in a public and academic private centre between 2012 to 2021. CT regimens for comparison included anthracyclines, taxanes, T and P. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NACT. DDFS was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis and a logistic regression to identify factors related to the first metastasis site. Results 372 patients with HER2 positive BC were included. Median age was 51 years (24 – 79), 57.5% were classified as Hormone Receptor positive (HR), and 4.5% were stage I, 48.2% stage II and 47.3% stage III. 65.8% were treated in a Public Hospital (PH) and 34.2% in an Academic Private Centre (AC). 85.2% received both anthracyclines and taxanes, 10.0% only taxanes and 4.8% only anthracyclines-based CT. 55 patients (14.8%) received both T and P, while 3.3% did not receive any HER2 directed therapy as NA treatment. Median T doses before surgery were 6 (1 – 12). pCR rate was 46.5% which varied according to HR expression: 61.0% in HR-positive BC vs. 36.2% in HR-negative disease (p=0.0001). pCR according to treatment were as follows: no-T no-P 22.2%, only-T 49.4%, both T-P 60.0% (p=0.02). We found no difference in pCR rate between anthracycline and non-anthracycline based CT (49.1% vs. 45.9%, p=0.72). With a median follow-up of 36 months, DDFS at 3 and 5 years differed regarding pathological response: 94.8% vs. 77.1% and 86.3% vs. 69.1% (p=0.0006), for pCR and non-pCR group, respectively. In a multivariate analysis, stage III vs. I-II (HR 2.5, p=0.005), non-pCR vs. pCR (HR 2.6, p=0.01) and not receiving NA anti-HER2 treatment (HR 2.6, p=0.01) were associated with higher risk of distant metastasis. Regarding recurrence, 7 out of 198 non-pCR tumors and 6 out of 174 pCR tumors presented brain metastasis (BM) as the first site of distant recurrence(p=0.96). In contrast, visceral metastasis (VM) as the first site of recurrence, were more frequent in non-pCR (21/198) than pCR patients (3/174, p=0.001). In a multivariate analysis, the only factor associated with BM was stage III (HR 5.8 vs stage I-II, p=0.02) and with VM was not achieving pCR (HR 6.3, p=0.02) and not using T nor P (HR 5.1, p=0.008). Conclusion The use of anti-HER2 treatment in a NA scheme is critical in HER2 positive disease. Although P is associated with increased pCR, we found no survival benefit with its use. Retrospective analysis, few events, post-surgical treatment might have influenced these results. Achieving pCR is associated with better prognosis by reducing distant recurrence but not BM. New strategies are needed to prevent the occurrence of this event. Citation Format: FRANCISCO ACEVEDO, Benjamin Walbaum, Lidia Medina, Tomas Merino, Catherine Bauerle, Mauricio Camus, Augusto Leon, Manuel Manzor, Paulina Veglia, Raul Martinez, Constanza Guerra, Marisel Navarro, Francisco Dominguez, CÉSAR SÁNCHEZ. The real-world outcome of human epidermal growth factor type-2 positive breast cancer patients receiving neoadjuvant therapy with or without pertuzumab [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-17.

Frequency and risk of adverse reactions to TB therapy in children and adolescents

Introduction.In the treatment of tuberculosis in children, the proportion of adverse events to therapy can be as high as 55 %, especially at the initial stages of treatment. Timely detection and monitoring of their development can improve the effectiveness of tuberculosis treatment.The aim of the workwas to study the peculiarities of adverse reactions in children and adolescents during antituberculosis therapy for their prediction and timely detection.Materials and methodsA retrospective cohort study including 243 patients aged 0 to 17 years who received treatment in two major institutions of Kemerovo Oblast – Kuzbass during 2018–2021 was conducted. Statistical processing of the material assessed risk factors for the development of adverse events in the groups with dyspeptic, toxic and allergic reactions.ResultsIn the course of chemotherapy 88 patients (36.2 %) developed adverse reactions: dyspeptic – in 55 patients (62.5 %), allergic – in 29 (32.9 %) and toxic – in 28 patients (31.8 %). Adverse reactions developed more often in children and adolescents with concomitant diseases of the gastrointestinal tract, in the presence of complaints before treatment for tuberculosis, during treatment on IV, V chemotherapy regimens with the presence of Pto, Pas, Lfx and Cm in the scheme, as well as when taking broad spectrum antibiotics and anti-tuberculosis drugs.DiscussionDespite the involvement in the process of identifying and monitoring the development of adverse reactions in TB treatment in children, the main risk factors for their development have not yet been identified. The study demonstrates the contribution to the development of adverse reactions of such factors as treatment on IV, V chemotherapy regimens, comorbid GI diseases, presence of complaints during hospitalization in a TB hospital and taking antibiotics together with antituberculosis drugs.ConclusionUndesirable phenomena were mostly observed at the start of antituberculosis therapy. Allergic, toxic and dyspeptic reactions occurred most frequently in the study group. The risk factors for their development were: IV, V chemotherapy regimens (OR = 2.5), presence of Pto (OR = 2.7), Pas (OR = 3.0), Lfx (OR = 2.3) and Cm in the CT regimen (OR = 3.8), comorbid GI diseases (OR = 3.5), complaints during hospitalization in the TB hospital (OR = 1.8) and taking antibiotics together with antituberculosis drugs (OR = 2.5).

Effects of Concurrent Strength and HIIT-Based Endurance Training on Physical Fitness in Trained Team Sports Players: A Systematic Review and Meta-Analysis.

Concurrent strength and HIIT-based endurance training (CT) has merit in time-saving in team sports. However, the effect of CT on physical fitness remained equivocal. This meta-analysis aimed to determine whether CT would produce an interference effect on the development of physical fitness when compared to strength training (ST) or HIIT-based endurance training (HET) alone in trained team sports players. A total of 2478 studies from three databases were screened. 52 full texts were reviewed. Seven studies were finally included and then subgroups were used for quantitative analysis. Compared to ST alone, CT had a significant effect on the development of maximal lower-body strength in trained team sports players (MD 4.20 kg, 95% CI 0.71-7.68, p = 0.02, I2 = 20%), but there was no significant difference between the groups on training adaptation in lower-body power (SMD 0.08, 95% CI -0.23-0.39, p = 0.62, I2 = 26%). Furthermore, a sub-group analysis based on the internal organization order of CT revealed that there was no statistically significant subgroup effect between CT and ST alone in all parameters. Well-designed CT regimens did not interfere with the development of physical fitness of trained team sports players.

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis.

BackgroundNeoadjuvant immune checkpoint inhibitor in combination with chemotherapy (nICT) or chemoradiotherapy (nICRT) has been tested in resectable esophageal cancer. Nevertheless, efficacy and safety for this new strategy have not been clearly demonstrated.Patients and methodsPubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible trials until June 30, 2022. The primary outcome of interest was pathological complete response (pCR). The random-effect model was used for statistical analysis.ResultsTwenty-seven trials with 809 patients were identified. The estimated rates of pCR for nICRT and nICT were comparable (32.7%, 95% CI: 20.3%-45.1% vs 26.3%, 95% CI: 19.8%-32.8%; P = 0.37). As for safety, surgical resection rate, R0 resection rate, surgical delay rate, and surgical mortality rate were similar between nICRT and nICT, while more grade ≥3 treatment-related adverse events were observed for nICRT (52.6%, 95% CI: 30.7%-74.5% vs 19.9%, 95% CI: 8.8%-31.0%; P = 0.01). In subgroup analysis, nICRT achieved higher pCR rate compared to nICT (56.2%, 95% CI: 41.0%-71.3% vs 27.2%, 95% CI: 20.2%-34.1%; P < 0.001) for squamous cell carcinoma (SCC) but adenocarcinoma. In patients receiving nICT, PD-L1 expression CPS ≥1 showed higher pCR rate compared to CPS <1 (51.3%, 95% CI: 41.4%-61.2% vs 26.6%, 95% CI: 8.6%-44.5%; P = 0.02); regimen of paclitaxel plus carboplatin/cisplatin (PC/TP) and 3-4 cycles of nICT did not lead to an significantly improved pCR rate compared to other chemotherapy regimens and 2 cycles of nICT, respectively, despite without increased toxicity.ConclusionBoth nICT and nICRT achieved promising pCR rates with acceptable tolerability, and nICRT was likely to have more antitumor efficacy compared to nICT for patients with SCC. PD-L1 status seemed to be predictive of pCR in patients receiving nICT; pCR rate did not appear to be greatly affected by CT regimen and increasing cycles of nICT.

The effect of breast radiotherapy parameters (XRT), chemotherapy regimens (CT) and dual anti-HER2 monoclonal antibodies (MoAb) on the development of cardiac dysfunction (CD) among patients with HER2-positive breast cancer from Saudi Arabia.

e12508 Background: Treatment with anti-HER2 therapy can cause CD. The effect of breast XRT, heart dose and V25 of the heart and CT regimen on developing CD is controversial. The impact of these variables in developing CD among patients with HER2-positive breast cancer (BC), receiving CT plus anti-HER2 MoAb was evaluated in routine clinical practice. Methods: Patients with HER2-positive BC between 2015-2019 were included, retrospectively. CD is defined as a drop in (EF%) of at least 10 % points from baseline and/or below 50% at any point of the time during follow-up. The association of CD and various variables was examined with a significance level of &lt; 0.05. Results: Data from 224 female patients were analyzed with a mean age at diagnosis of 51 +12, BMI 29.6 ± 6.4, BSA 1.74 ± 0.19, 53% with left BC, 63% had non-metastatic BC, 52% with comorbidities, 11% had prior IHD medication use in 48%; metformin in 15% and B-blockers in 5%, 9.4% smoker, 70% had a mastectomy, 18% lumpectomy and 12% no surgery, 58% received XRT. The cumulative incidence of CD was 33% during follow-up noting that the first and subsequent drops of EF at any point of time during the follow-up was counted as a new event even for the same patient. The univariate analysis of factors influencing the risk of CD is shown in Table. However, the initial significance of CT regimen and whether the patient received breast XRT or otherwise, did not translate into significance on multivariate analysis with a P-value = 0.198 &amp; 0.326, respectively. Conclusions: XRT mean heart dose and V25 of the heart, anthracycline-based CT did not influence the risk of CD among this cohort. Likewise, the dual anti-HER2 therapy with trastuzumab and pertuzumab and the number of trastuzumab cycles did not influence CD. It is reassuring to demonstrate the safety of these approaches in real-life clinical practice.[Table: see text]

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18–86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1–154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2–85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4–75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients’ multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Hair safe study: Effects of scalp cooling on hair preservation and hair regrowth in breast cancer patients receiving chemotherapy - A prospective interventional study

Hair safe study: Effects of scalp cooling on hair preservation and hair regrowth in breast cancer patients receiving chemotherapy - A prospective interventional study

Biomarker dynamics and prognosis in breast cancer after neoadjuvant chemotherapy

Breast cancer is a biologically diverse disease with treatment modalities selected based on tumor stage and tumor biology. Distinct intrinsic subtypes and surrogate biomarker profiles play a major role for therapeutic decisions. Response rates to systemic and local treatments as well as the interaction with epidemiological risk factors have been validated in clinical trials and translational studies. This retrospective study addresses the question how biomarker profiles and treatment modalities in the neoadjuvant chemotherapy setting have changed during the past 15 years and what prognostic impact these changes implicate. 342 female breast cancer stage I-IV patients receiving neoadjuvant chemotherapy between 2003 and 2017 were analyzed. Overall survival (OS) was correlated with preoperative clinical stage, postoperative pathological stage, treatment modalities and tumor biology before and after chemotherapy. Two subgroups were separated using an arbitrary cut-off year at 2009/2010, due to 2010 when platinum containing regimens were first administered. Median follow-up was 54 months. 57 (17%) patients died; recurrences occurred in 103 of 342 (30%) patients. Nodal stage and intrinsic subtypes (pre- and postoperative) significantly correlated with OS (p < 0.001). Preoperative histological grading lacked prognostic power. When comparing the patient characteristics of the subgroups, we found significant difference in the following characteristics: cT, ypT, ypN, pCR and chemotherapy regimens (p < 0.001). There was no difference in OS when comparing the two subgroups. Pathological complete response (pCR) rates had a significant impact on OS and disease-free survival (DFS) in HER2+ and triple negative subtypes (p = 0.03). In multivariate analysis, high proliferation index (> 30%), clinical metastatic stage and pathological tumor stage had prognostic impact on OS (p < 0.001, p = 0.0001, p = 0.002). Clinico-pathological factors and distinct therapy regiments especially in triple negative and HER2+ subtypes have prognostic impact on pCR, OS and DFS after neoadjuvant chemotherapy.

First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial

BackgroundThe EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. MethodsPatients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). ResultsOverall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40–0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50–0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. ConclusionsCHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. Clinical trial registration numberNCT02383966.

P-291 The prognostic and predictive factors for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the standard treatment for locally advanced rectal cancer (LARC). Despite of improvements of neoadjuvant treatments, local recurrence is still problematic. Besides well-known clinical prognostic factors, more reliable predictive factors must be identified for predicting treatment response and prognosis of LARC. We aimed to investigate the clinical, laboratory, radiological, and histopathological parameters that predict response to neoadjuvant therapy. A total of 51 patients with LARC who received neoadjuvant CRT between 2015-2018 in Antalya Training and Research Hospital were included in the study. Demographic characteristics of patients, pre-treatment laboratory parameters (CEA, CA 19-9, albumin, LDH, hemoglobin, lymphocyte count, thrombocyte count), grade, ulcer and necrosis in endoscopic biopsy materials, lymphovascular invasion (LVI) in resection materials after treatment, perineural invasion (PNI) presence, and degree of intratumoral lymphocytic response were examined. Post-operative tumor response rating was grouped according to the Modified Ryan Regression System. According to the pathological response status, numerical variables were compared with one-way analysis of variance. Frequency differences between pathological response grading were investigated by Chi-square test. Multivariate regression analyses were performed to reveal the factors predicting pathological responses. Survival analyses were performed using the Kaplan-Meier method. LARC pts who were treated with neoadjuvant CRT were included in the study. Median age was 64 ±12.4 (range 27-87) years. Clinical stage were T2 (21%), T3 (53%) and T4 (26%) and nod positivity rate was 77%. Pathologic grade was mostly grade 2. According to RECIST, ORR was 45.4%. According to Modified Ryan criteria; regression grade 0 and 1 (group 1: complete and near complete response) rate was 17.6 and 5.9%, grade 2 (group 2: partial response) was 51% and grade 3 (group 3: poor/no response) was 3.9%. Clinical characteristics, CT regimens and radiological response rates were similar between regression groups. 27.6% pts with radiological responders had no pathologic response. pN+ rate was 17% in the pts with good pathologic response. LVI rate was higher in the pts with group 3. NLR were similar between the 3 groups but TLR was different between groups 1 and 3 (p=0.015). TLR was higher than 135 in the pts with regression grade 2 and 3. According to regression analyses, PNI, NLR ≥2.8 and TLR ≥135 were independent predictive factors for regression grades. Median follow-up was 26 (range 3-97.2) months, median DFS was 19.58±4.6(95%CI:10.5-28.67) months. Median OS was not reached. Median DFS were similar between regression grades. However, regression grades, NLR and CEA were predictive factors for median DFS. In concordance with the literature, we concluded that neoadjuvant CRT enhances the tumor immunologic response. Initially high NLR and TLR were predictive factors for neoadjuvant treatment response in the pts with LARC. Initially high CEA levels, LVI and PNI were poor prognostic factors. Radiological responses cannot always be correlated with pathological responses. Not only the primary tumor, but also lymph nodes must be evaluated carefully.

Characterization of long-term responders following treatment with talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 embraca trial.

1029 Background: In the EMBRACA trial (NCT01945775), the poly(ADP-ribose) polymerase inhibitor (PARPi) TALA significantly improved progression-free survival (PFS) versus PCT in patients (pts) with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (BC) (8.6 vs 5.6 months [mo]; hazard ratio [HR, 95% CI] 0.54 [0.41-0.71]; P &lt; 0.0001). Predictive markers for response to PARPi, other than germline BRCA1/2 mutational status, are largely unknown. A previous analysis investigated biomarkers associated with long and short responders in EMBRACA. Here, we report the clinical characteristics of long and short responders. Methods: Pts were randomized 2:1 to TALA or PCT. In this retrospective analysis, pts in the intent-to-treat (ITT) population were mapped into two groups based on response: LONG (pts in TALA arm with overall survival [OS] ≥30 mo and duration of treatment ≥24 mo; pts in PCT arm with OS ≥30 mo); SHORT (pts in either arm with a PFS event [progressive disease by Independent Radiological Facility or death] ≤12 wks). Data cutoff date was Sept 30, 2019. Results: Of 431 pts randomized, 412 pts were treated (286 received TALA; 126 received PCT). In the ITT population, 37 pts receiving TALA and 34 pts receiving PCT were identified as LONG responders; 40 pts receiving TALA and 32 pts receiving PCT were SHORT responders. The Table shows a summary of pt characteristics for LONG and SHORT responders. More pts with HR+ BC and no prior CT for ABC were associated with LONG response; more pts with TNBC and ≥2 prior CT regimens or platinum were associated with SHORT response (Table). Median treatment duration for LONG responders (n = 37, TALA; n = 31, PCT) was 33.5 (24.0-61.4) mo for TALA and 7.6 (1.1-36.3) mo for PCT; 51.4% receiving TALA and 91.2% receiving PCT had subsequent therapy. In SHORT responders, median treatment duration was 2.0 (0.1-5.5) mo (TALA) and 1.4 (0.2-5.6) mo (PCT); 67.5% and 68.8% received subsequent therapy following TALA or PCT, respectively. Conclusions: In this clinical characterization of responders from the EMBRACA study, a higher number of LONG responders had HR+ BC and received no prior CT for ABC. A greater proportion of SHORT responders had TNBC and received ≥2 prior CT regimens or platinum. Further investigation is warranted in a larger number of pts. Clinical trial information: NCT01945775 .[Table: see text]

Abstract PD10-11: Efficacy of Platinum-based first-line chemotherapy among metastatic breast cancer (MBC) patients according to the germline BRCA1/2 mutational status: An analysis of the French ESME MBC database

Abstract Background: Platinum-based chemotherapy regimens (PtCT) have been shown to increase treatment efficacy when combined to neoadjuvant standard of care treatment of triple negative breast cancers (TNBC). In the metastatic breast cancer (MBC) setting, preclinical and clinical data suggest that PtCT could be more efficient than non-platinum based ones (non-PtCT) among patients (pts) with germline BRCA1/2 mutations (gBRCAm). However, published data remain controversial on this topic, particularly for MBC. We evaluated the progression-free (PFS) and overall survival (OS) under first-line PtCT and non-PtCT among gBRCAm carriers in ESME, a nationwide real-life MBC database. Methods: ESME MBC database (NCT03275311), is a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. Women with HER2- MBC and known hormone receptors (HR) and gBRCA1/2 (before or in the 6 first months of metastatic disease, gBRCAm / wild type / not tested) status, who received a first-line MBC CT were selected. Patients with other germinal mutations were considered as wild type. Primary objectives were OS and PFS under first-line CT (PtCT vs. non-PtCT) in the TNBC gBRCA1/2m population.Secondary objectives were OS and PFS during first-line CT (PtCT vs. non-PtCT) in the TNBC wild-type and “not tested” population, as well as among the HR+/HER2- pts.To avoid guarantee time bias related to oncogenetic testing, analyses were performed at baseline (CT initiation) and different landmark time points (3-month or 6-month after CT initiation). Thus, BRCA status was defined according to oncogenetic testings performed before the landmark time, and patients who progressed or censored before the landmark time were excluded. Results: 10,164 pts (2,794 TNBC; 7,370 HR+/HER2-) were included in this analysis. Pts who received PtCT were significantly younger, affected by a gBRCA1/2m, had a high histological grade and/or TNBC tumor, with more frequent visceral and central nervous system spreading than non PtCT ones. Median follow-up was 51.1 months [95%CI 49.6; 52.6]. All reported results were based on the gBRCA status defined at CT initiation and on multivariable analysis adjusted on age at MBC diagnosis, de novo MBC status, type and number of metastases. In the gBRCA1/2m TNBC population (N=132), PtCT was independently associated with a better PFS compared to non-PtCT (HR=0.56, 95%CI 0.38-0.84, p=0.005), without significant difference in OS (HR=0.79, 95%CI 0.51-1.23, p=0.29).No difference was seen in wild-type BRCA1/2 TNBC pts (N=269) according to the CT regimen, while, in the larger population of untested TNBC (N=2,393), PtCT was associated with worse OS (HR=1.18, 95%CI 1.03-1.34, p=0.016) compared to non-PtCT regimens, without significant difference in PFS (HR=1.07, 95%CI 0.95-1.22, p=0.26). No significant difference was seen regarding PFS nor OS in gBRCA1/2m HR+/HER2- pts (N=124) and in the wild-type BRCA1/2 HR+/HER2- population.However, in the larger population of untested HR+/HER2- pts (N=6,836), PtCT was independently associated with worse OS (HR=2.15, 95%CI 1.79-2.59, p&amp;lt;0.001) and PFS (HR=1.57, 95%CI 1.33-1.86, p&amp;lt;0.001) compared to non-PtCT regimens. Results were similar in landmark analyses at 3-month or 6-month after CT initiation. Conclusions: This large-scale real-life analysis suggests higher efficacy of PtCT in term of PFS in gBRCA1/2m TNBC pts. The small sample size and post-1st line treatments may preclude observing a significant OS difference. PtCT appeared however associated with worse outcomes in untested TNBC and HR+/HER2- pts. These results emphasize the need for BRCA1/2 characterization before considering these regimens in the MBC setting. Citation Format: William Jacot, Amélie Lusque, Audrey Mailliez, Thibault De la Motte Rouge, Luc Cabel, Christelle Levy, Anne Patsouris, Isabelle Desmoulins, Lionel Uwer, Marianne Leheurteur, Mathieu Robain, Olivier Caron, Thomas Bachelot, Thomas Filleron, Jean-Sébastien Frenel, Suzette Delaloge. Efficacy of Platinum-based first-line chemotherapy among metastatic breast cancer (MBC) patients according to the germline BRCA1/2 mutational status: An analysis of the French ESME MBC database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-11.

Upfront Therapy with Ibrutinib Results in a Longer Progression-Free Survival Independently of IGHV Mutational Status and Del(11q) in CLL Patients. Results of a Comprehensive Review and Meta-Analysis

Background: Recent studies have demonstrated a prolonged progression-free survival (PFS) in CLL patients receiving ibrutinib-based regimes as upfront therapy. These studies, however, are limited in number and heterogeneous regarding patients' selection criteria, treatment combinations and schedules. Because of this, we conducted a meta-analysis of randomized clinical trials using ibrutinib as upfront treatment to evaluate the strength of the evidence and patients' subgroups who benefit the most of such treatment. Materials &amp; Methods: A systematic literature search was performed using PubMed to identify full length reports dealing with the randomized clinical trials (RCTs) of ibrutinib, used alone or in combination as upfront therapy of CLL prior to August 2nd, 2019. A complementary manual search of the ASH, EHA and ASCO conference proceedings was also performed. The search strategy used both Medical Subject Headings (MESH) terms and free text words to increase the sensitivity of the search. The electronic search yielded 4 full-text articles assessed for eligibility. Results: In total 4 RCTs (i.e., RESONATE2, ALLIANCE, ILLUMINATE, ECOG-ACRIN) including 1574 untreated CLL patients compared head-to-head an ibrutinib-based regimen to CT or CIT. Inclusion criteria were either age 65 years or older or coexisting conditions for 1045 patients and age younger than 70 years in absence of coexisting conditions for 529 patients. Among patients treated with an ibrutinib-based regimen, 318 received ibrutinib as single agent and 649 ibrutinib in association with anti-CD20 monoclonal antibodies (i.e., 536 ibrutinib + rituximab [R], 113 ibrutinib + obinotuzumab [Obino]). The CT or CIT control arms included 607 patients and consisted of chlorambucil (CLB)(n=133), CLB+Obino (n=116), bendamustine and R (BR) (n=183) and fludarabine, cyclophosphamide and R (FCR)(n=175). All four studies included in the quantitative meta-analysis had enough data to assess PFS. Results indicate that treatment with ibrutinib-based regimens improved PFS compared with CT or CIT. The pooled HR for PFS in ibrutinib-treated patients was 0.331 (95% confidence interval [CI]: 0.272-0.403; P=0.000). The I2 statistic for heterogeneity (i.e. 0%; P=0.50) and Q values (i.e. 3.35) indicated a high level of homogeneity of results across studies. Of note, data were robust with no evidence of obvious publication bias (i.e., Funnel plot analysis indicate several missing studies that would bring p-value up to &gt;0.05=156). Overall survival (OS) was evaluated in 3 studies accounting for 1017 patients and revealed an HR of 0.289 (95% CI, 0.071-0.1175), with definite heterogeneity across studies (I2=82.7%; Q=11.6; P=0.003). Next, we evaluated the magnitude of improvement in PFS obtained with ibrutinib-based regimens in patients with high-risk genetic features such as 11q deletion and unmutated IGHV status. Data for PFS by 11q deletion status, restricted to 3 studies (n=206), revealed a significantly lower risk of progression for 11q deleted patients treated with ibrutinib-based regimens (HR,0.159; 95% CI: 0.077-0.327; I2 = 42%; P=0.18; Q = 3.46) (Fig 1A). Of note, a lower risk of progression was observed in both patients with unmutated (n=522) (HR, 0.178; 95% CI, 0.121-0.261; p=.000; I2=11%; Q=2.21;P=0.32)(Fig 1B) and mutated IGHV (n= 287)(HR, 0.270;95% CI, 0.149-0.489; I2=0%; P=0.38;Q=1.91)(Fig 1B) who received ibrutinib in upfront. Despite slight differences of the HR values between patients with mutated and unmutated IGHV, interaction analysis suggests that the magnitude of PFS improvement is comparable in both groups (HR, 1.50; 95% CI, 0.74-3.04; P=0.87). Conclusions This meta-analysis validates the notion that in comparison with CT or CIT ibrutinib-based regimens, given as upfront therapy, abrogate the negative impact of 11q deletion and unmutated IGHV on PFS. Even more, 11q deletion could be a favorable predictive biomarker for ibrutinib therapy. Because of design and selection criteria of studies included in this meta-analysis, some aspects such as the impact on response and its duration in patients with 17p deletion/TP53 mutations need further evaluation. Nonetheless, our results should inform updated algorithms of upfront CLL treatment. Figure 1 Disclosures Molica: Gilead, AbbVie, Jansen, Roche: Other: Advisory Board. Levato:Novartis: Honoraria; BMS: Honoraria; Incyte: Honoraria; Pfizer: Honoraria.

Dosimetric Analysis, Acute Toxicity and Long-Term Outcome of Craniospinal Irradiation Using Helical Tomotherapy in Children and Adults

To describe dosimetry, acute toxicity, long-term survival and risk of second malignancies in children and adults treated with helical Tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2019, 58 pts (age 2-47 years, median 14) were treated with HT-CSI. The most common histologies were medulloblastoma (n = 40), CNS embryonal tumor NOS (formerly PNET) (n = 9) and intracranial GCT (n = 3). Other neoplasms were ATRT, ependymoma, glioma and ALL. 33 pts (57%) presented with distant dissemination or liquoral involvement. Among non-metastatic pts, a gross total resection was not achieved in 36% of cases. The prescribed HT-CSI doses were 23.4-36 Gy (1.6-1.8 Gy/fr) according to age-, tumor- and stage-specific protocols. Cases were contoured at one Pediatric Radiation Oncology Unit according to pediatric RT guidelines. Adjuvant, concurrent/adjuvant, neoadjuvant, neoadjuvant/adjuvant and no CT was administered in 31%, 17%, 17%, 23%, 12% of pts, respectively. A dosimetric analysis for PTVs and OARs was performed. Acute side effects were recorded according to the CTCAE 4.0. Survival analysis was performed by the Kaplan–Meier method. 3 cases of acute cerebral edema were reported in pts with massive intracranial disease and spinal involvement with implanted shunts. Considering only 39 pts not receiving CT or in complete recovery from mielotoxicity prior to HT-CSI, hematological toxicity included G1-4 leukopenia (5%, 18%, 41%, 15%, respectively), neutropenia (21%, 21%, 31% and 8%), thrombocytopenia (41%, 10%, 10% and 10%) and anemia (39%, 13%, 3% and 3%). No other G3–4 toxicity was reported. Apart from alopecia, the other most common G1-2 acute toxicities were nausea/vomiting (58% of pts), dermatitis (28%), anorexia/asthenia (14%), dysphagia (12%) and stomatitis (10%). The 3-, 5- and 10-year OS was 76%, 64% and 49%, respectively. Apart from 4 pts showing progression despite therapy, relapse after HT-CSI occurred in 18 pts. Rates of 3-, 5- and 10-year PFS from the end of RT were 59%, 56% and 41%, respectively. No second primary cancer occurred. Survival for pts with medulloblastoma included 3-, 5- and 10-year OS of 88%, 77% and 63%, respectively, and 3-, 5- and 10-year PFS of 77%, 67% and 60%, respectively. In the medulloblastoma group the 10-year OS/PFS resulted 53/54%, 67/75% and 91/59% for pts <=14, 14-25 and >25 years-old, respectively. M-status, surgical resection extension and CT regimen seemed to be associated to survival in an age-dependent manner. HT-CSI acute toxicity was in line with Literature. Further efforts to correlate dosimetric and toxicity data are needed. Long-term survival for pts with medulloblastoma resulted related to age. Older pts seemed to benefit from not receiving reduced-dose RT and different CT regimens. At a follow-up up to 11.5 years from the end of HT-CSI, no second malignancy occurred.

The Effect of Neoadjuvant Radiotherapy on Tumor Regression Grade in Resected Pancreatic Adenocarcinoma

Histopathologic tumor response to neoadjuvant therapy is associated with improved outcomes in pancreatic cancer. The optimal neoadjuvant regimen remains unclear. We sought to compare response to neoadjuvant chemotherapy alone (CT) or CT combined with radiotherapy (RT). A retrospective review of a single institution database was performed. Patients diagnosed with pancreatic cancer (PCA) between 2009-2018 undergoing neoadjuvant CT, with or without subsequent RT, and definitive surgical resection were included. Resection specimens were assigned a tumor regression grade (TRG) using the College of American Pathologists criteria. TRG scores of 0 (complete response) and 1 (near complete response) were combined for analysis. Clinical and treatment variables associated with TRG were assessed. The impact of TRG on relapse free survival (RFS) was evaluated using the Kaplan-Meier method. Of the 74 patients who met inclusion criteria, 35 were treated with neoadjuvant CT and 39 underwent CT followed by RT. Median FU was 13.3 mos and 95% had borderline resectable or locally advanced PCA. The CT regimen was FOLFIRINOX or Gemcitabine-nab-paclitaxel in 93% of patients. In the RT subgroup, 41% (n=16) received SBRT with a median dose of 36 Gy in 3 fractions; all others received fractionated RT with median dose 50.4 Gy in 28 fractions. The median time from RT to surgery was 1.6 months (IQRT 1.3 – 1.9 mos). The rate of TRG scores of 0-1, 2 (mixed response), and 3 (poor or no response) for the CT group was 11%, 34%, and 54%, respectively, and for the RT group the corresponding rates were 31%, 44%, and 26%, respectively (p=0.02). Seven patients were scored TRG 0 (9%), and the majority (n=6) had received RT. On multivariate logistic regression, RT remained associated with TRG when controlling for CA19-9, age, and initial tumor size (p=0.01). In the RT subgroup, receipt of SBRT, prescribed biological equivalent dose (BED [Gy10]), and min GTV BED were not associated with TRG. As expected, worse TRG was associated with higher lymph node ratio (p<0.01) and positive surgical margins (p=0.03). The association of TRG and RFS trended toward significance (p=0.07); median RFS was not reached in TRG 0-1 and it was 18 mo and 9 mo in TRG 2 and 3, respectively. Compared to neoadjuvant CT alone, neoadjuvant CT followed by RT is associated with greater histopathologic response in PCA.