Duration Of Chemotherapy Research Articles

Comparative analysis of anti-relapse treatment regimens in 110 patients with hepatic and pulmonary hydatid echinococcosis.

Hydatid echinococcosis is worm disease caused by Echinococcus granulosus, that is primarily detected in the liver and lungs. This study aimed at determining the clinical tolerance and efficacy of albendazole in patients with cystic echinococcosis, depending on the volume of the previous one. We retrospectively (from 2016 to 2020 years) analyzed patients who have been treated with two treatment regimens (28-day courses with a 14-day break and continuous drug intake for 60 days), which are used in the Russian Federation. There were 110 patients (after surgery) who had hydatid echinococcosis of the liver and lungs; the diagnosis of these patients was confirmed morphologically (intra-vitam). A retrospective analysis was carried out on the following matters: (1) the duration of anti-relapse chemotherapy depending on the localization of the parasitic cyst; (2) chemotherapy's side effects and long-term relapses after treatment. We evaluated patients' tolerability of albendazole according to the level of blood cells count and hepatic enzymes. The effectiveness of anti-parasitic treatment was evaluated by imaging studies that did not reveal the growth of new parasitic cysts even in the presence of serum antibodies to echinococcal antigens. A correlation was found between the choice of antiparasitic treatment regimen and the frequency of adverse reactions in lab tests: more often adverse reactions (drug-induced hepatitis, anemia, granulocytopenia) occurred in patients who received a continuous treatment regimen for 60 days (p < 0.05). The frequency of relapses reached 4.5% and was more often observed in patients who received treatment for 28 days with a 14-day break. Continuous drug intake for 60 days is the most effective.

GYNECOLOGICAL MALIGNANCIES

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)

Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Early Onset Pancreatic Cancer: Clinical Outcomes and Toxicity

<h3>Purpose/Objective(s)</h3> Little is known on optimal management of patients with early onset pancreatic cancer (EOPC), including the role of radiation therapy. As such, we report on a cohort of patients with EOPC (age <55 years) who was treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). <h3>Materials/Methods</h3> This was a single institution retrospective review of patients with EOPC who were treated with upfront chemotherapy followed by SBRT with or without surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Next-generation sequencing (NGS) was performed on select patient tumor specimens. <h3>Results</h3> From 2016-2021, 47 patients met the inclusion criteria. Median age was 50.4 years (range, 36.4 – 54.7 years). Median induction chemotherapy duration was 4 months (range, 2.5 – 9 months). The majority (46/47, 97.9%) of patients received 33 Gy in 5 fractions. Following SBRT, 43 patients (91%) underwent surgical exploration, with extent of vascular involvement on post-SBRT imaging precluding exploration in 4 patients (9%). Gross resection was achieved in 33 patients (70.2%), with intraoperative metastatic disease precluding resection in 8 patients (17%) and intraoperative extent of vascular involvement of the primary tumor precluding resection in 4 patients (9%). Median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (≥ 4 months) was associated with improved median OS (16.5 vs 10.1 months, p=0.005), LPFS (10.1 vs 4.9 months, p=0.002), DMFS (9.7 vs 5.2 months, p=0.014), and PFS (9.7 vs 5.2 months, p=0.020). Normalization of CA 19-9 (≤ 34 vs > 34 U/ml) after chemotherapy was associated with improved median DMFS (not reached vs 5.6 months, p=0.003) and PFS (11.3 vs 5.6 months, p=0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. Clavien-Dindo 3b toxicity rate was 3.0%. A total of 15 patients underwent NGS, with mutations being found in <i>KRAS</i> (10/15, 66.7%), <i>TP53</i> (7/15, 46.7%), <i>NOTCH 1/2</i> (3/15, 20%), <i>CDK2NA</i> (2/15, 13.3%), and <i>SMAD4</i> (1/15, 6.7%). <h3>Conclusion</h3> Multi-modality therapy for EOPC was administered with low toxicity, but outcomes remain suboptimal. Induction chemotherapy duration ≥ 4 months and normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population, such as radiation dose escalation, expansion of the radiation target volume, and more aggressive surgical techniques.

The Optimal Timing of Surgery Following Stereotactic Body Radiation Therapy for Borderline Resectable or Locally Advanced Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> In patients undergoing pre-operative stereotactic body radiotherapy (SBRT) for borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), the optimal timing of surgery following SBRT is unknown. We aimed to assess the impact of time from SBRT to surgery on outcomes in this setting. <h3>Materials/Methods</h3> Patients treated at a single institution with BRPC/LAPC, who underwent neoadjuvant multi-agent chemotherapy followed by SBRT, and then surgical resection, were included in this analysis. Covariates were stratified by time from SBRT to surgery. Pearson's Chi-squared test was used to compare cohorts by time from SBRT to surgery with respect to baseline and treatment characteristics. A Cox regression model was used to identify variables associated with survival outcomes, with statistically significant covariates in univariable analysis included in multivariable modeling. <h3>Results</h3> One hundred seventy-one patients were ultimately included for analysis. The median time from SBRT to surgery was 6.4 weeks (range: 2.7 – 25.3, IQR 2.7 weeks). There was no statistically significant difference in age, sex, tumor location, neoadjuvant chemotherapy type (FOLFIRINOX vs gemcitabine/nab-paclitaxel) or chemotherapy duration >4 months, pathologic complete response (pCR) rates, or R0 resection rates by time from SBRT to surgery, using a 6-week cutoff. Local progression-free survival (LPFS) was higher in patients for whom time from SBRT to surgery was >6 weeks (1-yr LPFS 81.5% vs 70.2%, median LPFS 12.1 vs 10.8 months, log-rank P=.039). No difference in distant metastases-free survival or overall survival was detected. In univariable Cox regression, age, SBRT dose, neoadjuvant chemotherapy duration/type, tumor location, presence of pCR, and surgical margin status were not associated with LPFS, but time from SBRT to surgery less than 6 weeks (P=.042; HR 1.84 95% CI 1.02 – 3.30) and baseline elevated CA19-9 >200 U/mL (P=.018; HR 2.09, 95%CI 1.14 – 3.84) were significantly associated with reduced LPFS. In multivariable analysis, time from SBRT to surgery < 6 weeks (P=.011; HR 2.18, 95% CI 1.19 – 3.97) and baseline elevated CA19-9 (P=.006; HR 2.38, 95% CI 1.28 – 4.42) remained independently associated with reduced LPFS. Sensitivity analysis was performed excluding patients who had surgical resection >15 weeks after completion of SBRT (n=4). Time from SBRT to surgery <6 weeks and elevated baseline CA19-9 remained independently associated with reduced LPFS. <h3>Conclusion</h3> Prolongation of time from SBRT to surgery may be associated with improved local progression free survival. Further study is warranted to understand the factors that may contribute to differential local control rates based on time from SBRT to surgery.

Cox Proportional Hazard Regression Interaction Model and Its Application to Determine The Risk of Death in Breast Cancer Patients after Chemotherapy

Introduction: This research is based on medical record data of breast cancer patients who seek treatment at the Central General Hospital, dr. Sardjito Yogyakarta, from 2018-2021 has as many as 105 patients. Several risk factors for cancer include demographic factors, clinical factors, tumor factors, and therapy. These factors lead to different psychological states of patients, resulting in the rate of recovery and death of patients.&#x0D; Objective: To determine the risk of death in breast cancer patients after chemotherapy.&#x0D; Methods: The method used in this study is Cox Proportional Hazard survival analysis with an interaction model. The variables studied were age, marital status, profession, insurance, BMI, comorbidities, duration of chemotherapy, chemotherapy agent, chemotherapy type, and tumor size.&#x0D; Results: The analysis results using SPSS software obtained the best hazard and survival model with four significant variables, namely the duration of chemotherapy, chemotherapy agents, chemotherapy types, and the interaction between BMI and chemotherapy types.&#x0D; Conclusions: The most significant risk factor for death was palliative chemotherapy type with HR 27.195 and 3-5 chemotherapy agents with HR 4.997. Meanwhile, the long duration of chemotherapy and the interaction between lean BMI and palliative chemotherapy reduced the risk of death by HR 0.967 and 0.128, respectively.

Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer.

Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation. This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples. An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007). This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).

The Impact of Colon Cancer Sites on Survival Rates after Curative Resection and Adjuvant Chemotherapy: A SingleCenter Study

Background: Most recent studies indicate that right-sided colon cancer is associated with a significantly higher mortality rate. Multivariate analyses showed that the patient’s age, sex, mode of presentation, co-morbidity, and the stage had significantly influenced their survival. Although the primary tumor location has an impact on the overall survival in metastatic settings, the laterality of early-stage colon cancer might also affect the disease-free survival and determine the duration of adjuvant chemotherapy for each side. This study aimed to compare overall survival and disease-free survival between left-sided and right-sided high-risk stage II and stage III colon cancer in patients from a single institute. Methods: This retrospective cohort study was conducted between January 2004 and December 2017. Data on 153 patients who underwent curative resection and adjuvant chemotherapy for colon cancer were retrieved from an existing database. Results: We found that the five-year disease-free survival rates were 63.20% for left-sided colon cancer and 51.11% for right-sided colon cancer (P-value &lt; 0.05). The five-year overall survival rates were 66.98% for left-sided colon cancer and 57.77% for right-sided colon cancer (P-value 0.063). The right-sided primary tumor location was associated with a significantly higher mortality rate (HR: 2.28; 95%CI 1.38–5.8; P-value: 0.004). Conclusion: The results of this study confirmed that patients with high-risk stage II and stage III colon cancer who had right-sided tumors were significantly more likely to have decreased disease-free survival and overall survival. Further prospective studies should focus on tumor genetics and proper durations of adjuvant chemotherapy to maximize the benefit of treatment with acceptable toxicity.

Effect of preoperative biliary stent on postoperative complications after pancreaticoduodenectomy for cancer: Neoadjuvant versus upfront treatment

BackgroundLimited data are available regarding the effect of preoperative biliary stent, during long-course neoadjuvant chemotherapy, on postoperative complications. The aim of the study is to analyze whether the association of neoadjuvant chemotherapy and biliary stent increases overall and infectious complications after pancreaticoduodenectomy. MethodsData for 538 consecutive pancreatic ductal adenocarcinoma patients who underwent pancreaticoduodenectomy between 2015 and 2020 were retrospectively analyzed. Four groups of patients were identified: neoadjuvant chemotherapy + biliary stent (171 patients), neoadjuvant chemotherapy–no biliary stent (65 patients), upfront surgery + biliary stent (184 patients), and upfront surgery–no biliary stent (118 patients). Median neoadjuvant chemotherapy duration was 6 months. The main outcome of the study was the occurrence of postoperative infections. ResultsNo differences among the 4 groups were observed for pancreaticoduodenectomy-specific complications (ie, POPF, DGE, PPH). Infectious complications, in particular surgical site infections, were more frequent in neoadjuvant chemotherapy + biliary stent group (P = 0.001). At multivariate analysis, biliary stent was significantly associated with postoperative infectious complications in the overall cohort (odds ratio 1.996, confidence interval 95% 1.29–3.09, P = .002) and in neoadjuvant chemotherapy patients (odds ratio 5.974, 95% confidence interval 2.52–14.13, P < .001). Biliary stent significantly increased the comprehensive complication index by 9.5% (95% confidence interval 0.04–0.64, P = 0.024) in the overall cohort and 18.9% (95% confidence interval 0.22–1.23, P = .005) in the neoadjuvant chemotherapy group. The presence of multidrug-resistant microorganisms in intraoperative bile culture was not influenced by long-course neoadjuvant chemotherapy. ConclusionIn neoadjuvant chemotherapy patients, biliary stent increased the occurrence of postoperative infectious complications and surgical site infections, while the incidence of multidrug-resistant bacteria in intraoperative bile culture was similar between groups.

Impact of chemotherapy during pregnancy on fetal growth

Background Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight <10th percentile). Limiting research to birth weights only might misjudge fetal growth restriction (FGR) in this high-risk population with multiple risk factors for impaired fetal growth. Moreover, the role of the duration of chemotherapy and gestational age at initiation of chemotherapy in fetal growth is yet poorly understood. Objective This retrospective cohort study evaluates fetal growth and neonatal birthweights in pregnant women receiving chemotherapy. Study design All pregnant patients, registered by the International Network of Cancer, Infertility and Pregnancy (INCIP), treated with chemotherapy with at least two ultrasounds reporting on fetal growth, were eligible for this study. Duration and gestational age at initiation of chemotherapy were our major determinants, followed by cancer type and stage, maternal characteristics (parity, BMI, ethnicity hypertension, and diabetes) and individual cytotoxic agents (anthracycline, taxanes, and platinum). Fetal growth outcomes were described using the following mutually exclusive groups (1) FGR, based on a Delphi consensus (2016); (2) “low risk SGA” (birth weight below the 10th percentile), but an estimated growth above the 10th percentile; (3) “fetal growth disturbance”, which did not meet all FGR criteria; (4) “non-FGR”. Obstetric and oncological characteristics were compared between the growth impaired groups and non-FGR group. We calculated estimated fetal weight (EFW) according to Hadlock’s formula (1991) and birth weight percentile according to Nicolaides (2018). We used univariable and multivariable regression, and linear mixed effect models to investigate the effect of duration and gestational age at initiation of chemotherapy on birth weight, and fetal growth, respectively. Results We included 201 patients, diagnosed with cancer between March 2000 and March 2020. Most patients were diagnosed with breast cancer (n = 132, 66%). Regimens included anthracyclines (n = 121, 60%), (anthracyclines and) taxanes (n = 45, 22%) and platinum (n = 35, 17%). Fetal growth abnormalities were detected in 75 pregnancies: 43 (21%) FGR, 10 (5%) low risk SGA and 22 (8.5%) fetal growth disturbance. Chemotherapy prior to 20 weeks of gestation (47% vs. 25%, p = .04) and poor maternal gestational weight gain (median percentile 15 (range 0–97) vs. 8 (0–84), p = .03) were more frequent in the FGR group compared to the non-FGR group, whereas no difference was seen for specific chemotherapy or cancer types. Univariable regression identified gestational weight gain, hypertension, systemic disease, parity, neonatal sex and maternal BMI as confounders for birth weight percentiles. Multivariable regression revealed that each additional week of chemotherapy was associated with lower birth weight percentiles (–1.06; 95%CI −2.01; −0.04; p = .04), and that later initiation of chemotherapy was associated with an increase in birth weight percentile (1.10 per week; 95%CI 0.26; 1.95; p = .01). Each additional week of chemotherapy was associated with lower EFW and abdominal circumference (AC) percentiles (–1.77; 95%CI −2.21; −1.34, p < .001; −1.64; 95%CI −1.96; –1.32, p < .001, respectively). Conclusions This study demonstrates that FGR is common after chemotherapy in pregnancy, and that the duration of chemotherapy has a negative impact. Sonographic follow-up of fetal growth and well-being is recommended.

The increasing indications of FDG-PET/CT in the staging and management of Invasive Bladder Cancer.

The management of locally advanced muscle invasive bladder cancer (MIBC) often necessitates neo-adjuvant chemotherapy (NAC) to eliminate any micro-metastatic disease prior to definitive radical cystectomy (RC) and pelvic lymph node dissection (PLND). The most common imaging techniques traditionally used during this process are computerised tomography (CT) and magnetic resonance imaging (MRI), both of which lack a high sensitivity for nodal staging. In this paper, we attempt to review the evolving indications of F-fluoro-2-deoxy-D-glucose positron emission tomography/computerised tomography (FDG-PET/CT) imaging, in the pre-clinical and post-treatment staging of bladder cancer, with a focus on its ability to evaluate response to NAC. We concluded that use of FDG-PET/CT allows for improved nodal staging and metastatic disease detection, compared to traditional imaging modalities. This enabled earlier detection of tumour response to NAC and/or residual disease, impacting factors such as duration of chemotherapy, with its associated adverse effects, and timing of surgical intervention. However, further studies are required to reliably assess its impact on both overall and disease-free survival.

THE COURSE OF TOXIC HEPATITIS IN LEUKEMIC PATIENTS AT THE STAGE OF SUPPORT THERAPY.

One of the main tasks in the treatment of acute leukemia is to prevent the development of complications of chemotherapy, as well as the timely choice of the correct tactics for the treatment of complications. Because forced breaks associated with complications negatively affect the end result of leukemia treatment. Practice shows that one of the organs affected by chemotherapy is the liver, and its damage directly depends on the toxicity and duration of chemotherapy. Our task was to conduct research work in this area, and to study toxic liver lesions in patients with leukemia. Before that, we carried out similar work at the stages of induction and consolidation of treatment of acute leukemia in children. And this period of research work is devoted to the supportive stage of therapy in patients. Objective: To study the frequency of toxic liver damage in children with acute leukemia during support therapy, to choose treatment tactics according to the severity of toxic hepatitis. The study group included 51 children with primary acute lymphoblastic leukemia who completed the induction stage with complete remission and retained this result for the entire period of consolidation. The age of the patients ranged from 2.5 years to 15 years. Of these, there were 28 boys and 23 girls. The patients were from Baku and the regions of the republic. Treatment of acute lymphoblastic leukemia was carried out according to two branches of the Moscow – Berlin – 2015 program: B and T İmRG. The protocols of maintenance therapy of these branches do not differ, and both begin with the 31st week of the general program, end on the 104th. Each protocol consists of 8 stages of a combination of chemotherapy drugs Metotreksat + 6-Mercaptopurine, which last for 6 weeks and alternate with two-week courses of reinduction - Deksametazon + Vinkristin. Before the start of maintenance therapy, all patients with leukemia confirmed the preservation of the previously achieved remission, and the functional and organic state of the liver. With positive results, the continuation of leukemia treatment began. And when the symptoms of toxic hepatitis were detected, the severity was determined. According to this indicator, 3 forms of flow were issued: light, medium-heavy and heavy forms. The tactics of conducting therapy of each form were chosen by us. Of 51 patients, 42 had toxic hepatitis (82%). It was mild in 12 patients (23.5%), moderate in 26 children (50.9%), and severe in 4 children (7.8%). In the mild form of hepatitis, patients were prescribed intravenous administration of Riboksin + Aevit (orally) for 10-14 days, or alternatively, per os Ursobil + Aevit. This combination made it possible to restore all clinical and laboratory parameters in patients within 14-21 days, and at the same time, without interrupting chemotherapy. Moderate and severe forms of hepatitis occurred mainly during the period of reinduction (54.7%). The administration of intravenous adeomethionine (Heptral) in the form of monotherapy for 8-12 days allowed continuous reinduction courses. Following him, the administration of an oral combination of Ursobil + Lipoic acid + Aevit for 14-21 days allowed to preserve the long-term effect. In severe hepatitis, chemotherapy was suspended, and patients were prescribed intravenous adeomethionine (Heptral) in combination with oral Ursobil + Aevit for 10-14 days, and along with this detoxification therapy was carried out in parallel. Such treatment gave an improvement in clinical and laboratory parameters. Subsequently, intensive therapy was suspended, and chemotherapy was started accompanied by Ursobil + Aevit + Lipoic acid for the next two weeks. This choice of therapy allowed us to preserve the restored indicators for a long time. There were no deaths or severe complications from toxic hepatitis in any case.

Association of clinic type with receipt of neoadjuvant therapy among patients with localized pancreatic cancer: Value of multidisciplinary clinic.

63 Background: Patients with localized pancreatic adenocarcinoma (PDAC) generally benefit from multi-modality therapy, which may be best coordinated through a pancreas multi-disciplinary clinic (PMDC). Whether treatment practice patterns vary based on whether a patient was seen through PMDC versus individual specialty-specific clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients who came to Johns Hopkins Hospital through either PMDC or one of the individual surgical, medical, or radiation oncology clinics for localized PDAC between 2018-2020 and eventually underwent resection. During this time, it was standard practice for borderline resectable (BRPC) patients to undergo at least 4 months of neoadjuvant chemotherapy, with or without radiation, before transitioning to exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation, followed by potential exploration. The primary outcome was completion of neoadjuvant therapy as per the above stage-specific institutional standards. Multivariable analyses were performed to find association between PMDC visit and completion of neoadjuvant therapy, controlling for age, sex, race, stage, baseline performance status and type of chemotherapy. Results: A total of 240 patients met inclusion criteria. Of these, 157 (65.4%) had PMDC visits. Distribution of stage across the cohort included 81 (34.3%), 91 (38.5%), and 64 (27.1%) patients with resectable PDAC, BRPC and LAPC, respectively. Patients in the PMDC group received radiation therapy more commonly (59.7% vs 34.9%, p = 0.004), as compared to patients seen through individual specialty-specific clinics. Mean duration of chemotherapy was higher for patients seen through PMDC (4.4 (SD: 1.7) vs 3.9 (SD: 2.0) months) compared with individual clinics. Completion of neoadjuvant therapy per institutional stage-specific standards was seen in 46% (n = 24) of the patients visiting individual specialty-specific clinics compared to 71% (n = 85) of patients who were seen through PMDC (p = 0.002). The adjusted odds ratio of completion of neoadjuvant therapy per institutional standards for patients seen through PMDC visit was 3.35 times the odds for patients seen through individual clinics (95% CIs 1.46-7.07; p = 0.004). Of note, a higher proportion of patients who were seen through PMDC enrolled in a clinical trial (n = 26, 16.6%) compared with patients seen through individual clinics (n = 6; 7.2%) (p = 0.043). Conclusions: Provision of care through a multi-disciplinary clinic was associated with significantly higher odds of completing neoadjuvant therapy per institutional standards as compared to care through individual specialty-specific clinics. In addition, care through a PMDC may also be associated with increased trial enrollment.

New and Persistent Sedative-Hypnotic Use After Adjuvant Chemotherapy for Breast Cancer.

Sedative-hypnotic medications are used to treat chemotherapy-related nausea, anxiety, and insomnia. However, prolonged sedative-hypnotic use can lead to dependence, misuse, and increased health-care use. We aimed to estimate the rates at which patients who receive adjuvant chemotherapy for breast cancer become new persistent users of sedative-hypnotic medications, specifically benzodiazepines and nonbenzodiazepine sedative-hypnotics (Z-drugs). Using the MarketScan health-care claims database, we identified sedative-hypnotic-naïve patients who received adjuvant chemotherapy for breast cancer. Patients who filled 1 and more prescriptions during chemotherapy and 2 and more prescriptions up to 1 year after chemotherapy were classified as new persistent users. Univariate and multivariable logistic regression analyses were used to estimate odds of new persistent use and associated characteristics. We identified 22 039 benzodiazepine-naïve patients and 23 816 Z-drug-naïve patients who received adjuvant chemotherapy from 2008 to 2017. Among benzodiazepine-naïve patients, 6159 (27.9%) filled 1 and more benzodiazepine prescriptions during chemotherapy, and 963 of those (15.6%) went on to become new persistent users. Among Z-drug-naïve patients, 1769 (7.4%) filled 1 and more prescriptions during chemotherapy, and 483 (27.3%) became new persistent users. In both groups, shorter durations of chemotherapy and receipt of opioid prescriptions were associated with new persistent use. Medicaid insurance was associated with new persistent benzodiazepine use (odds ratio = 1.88, 95% confidence interval = 1.43 to 2.47) compared with commercial or Medicare insurance. Patients who receive sedative-hypnotic medications during adjuvant chemotherapy for breast cancer are at risk of becoming new persistent users of these medications after chemotherapy. Providers should ensure appropriate sedative-hypnotic use through tapering dosages and encouraging nonpharmacologic strategies when appropriate.

Analysis of treatment outcomes according to the cycles of adjuvant chemotherapy in gastric cancer: a retrospective nationwide cohort study

BackgroundOne-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service.MethodsA total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy.ResultsThe five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74–4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65–3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84–2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39–1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84–3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11–3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76–2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35–1.96, P < 0.0001; ≥ 8 cycles: 67.2%).ConclusionsReducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.

329P Duration of adjuvant therapy in stage III colon cancer: A real world multi-institutional US-based experience

Since the publication of IDEA, the duration of adjuvant chemotherapy (CTX) in stage III colon cancer (CC) has shifted to a risk-stratified approach as 3 months (mo) of CAPOX vs 6 mo was found to be non-inferior in patients (pts) with low risk (LR) (T1-T3/N0-N1). High risk (HiR) (T4 or N2) disease failed to show non-inferiority, however 3-year DFS differences were less than 2% and only .1% when pts received CAPOX. However in the US cohort, pts did not receive CAPOX, possibly due to capecitabine intolerance. Herein, we performed a real-world evaluation of CTX in US pts with stage III CC. A retrospective review of stage III CC pts treated from 2016-2022 from 5 US academic medical institutions was performed. Pts were stratified into 3mo vs 6mo of CTX, HiR vs LR, and CAPOX vs FOLFOX. 3-year DFS and adverse events were recorded. A total of 443 pts were included. In the overall population, no difference in 3-year DFS was observed in 3 vs 6 mo of CTX (69.3 vs 71.0%, hazard ratio [HR] = 1.26, 95% CI (0.74, 2.17), adjusted p [aP] = 0.40), numerically less than was observed in IDEA. HiR pts were observed to have detriment in 3-year DFS with 3mo vs. 6mo CTX (34.0% vs 62.9%, HR = 1.51, 95% CI (0.77, 2.99), aP=0.23). Grade 3 adverse events (AE) of nausea, diarrhea, and hand/foot syndrome from capecitabine were higher than reported in IDEA.Table: 329PDFS by treatment, duration and riskCTXN (Events)36 Months DFS6 mo FOLFOX255 (76)71.8%6 mo CAPOX54 (17)67.5%3 mo FOLFOX37 (9)68.8%3 mo CAPOX97 (16)69.4%HiR vs LR6 mo LR126 (23)82.3%6 mo HiR183 (70)62.9%3 mo LR102 (13)81.2%3 mo HiR32 (12)34.0% Open table in a new tab In this real-world experience we observed no DFS benefit in pts treated with 3 vs 6mo CTX. In HiR pts treated with 3mo CTX, we observed a lower 3-year DFS rate compared to 6mo of CTX. The findings were not statistically significant due to low number of events in this cohort and was significantly lower than reported in IDEA. AEs were more prevalent in US pts compared to non-US pts in IDEA, likely due to capecitabine intolerance. Our study is the first to assess 3mo vs 6mo capecitabine based adjuvant CTX in a risk stratified US population and suggests discrepancies in DFS and AEs compared to IDEA in US pts who received CAPOX.

Risk factors associated with nausea and vomiting in children with cancer receiving chemotherapy.

Despite treatment with antiemetic medications, nausea remains uncontrolled for many children receiving chemotherapy. One reason is that risk factors for nausea in children remain poorly explored. The purpose of this study was to identify risk factors for chemotherapy-induced nausea (CIN) in children. Prospective, observational study including 101 children (median age 6.4 years, range 0.8-17.9) with cancer receiving moderately or highly emetogenic chemotherapy. Primary endpoints were complete control of acute and delayed CIN, defined as no nausea in the acute phase 0-24 h after chemotherapy and in the delayed phase starting after the acute phase and ending 5 days later. Multivariable analyses included age, sex, cancer type, susceptibility to motion sickness, chemotherapy duration, numbers of antiemetics, co-administration with opioids or tricyclic antidepressants, and previously uncontrolled nausea or vomiting. Acute CIN was associated with susceptibility to motion sickness (odds ratio [OR] 5.73, 95% confidence interval [CI] 1.36-33.7) and older age (OR 4.19, 95% CI 1.30-14.7), comparing age group 8-18 years with 0-3 years. Delayed CIN was associated with uncontrolled acute nausea or vomiting (OR 10.3, 95% CI 2.65-50.9), highly emetogenic chemotherapy (OR 8.26, 95% CI 1.17-76.8), and having a hematologic cancer type (OR 7.81, 95% CI 1.05-79.2). Susceptibility to motion sickness and age can influence the risk of acute CIN. More research is needed on how best to integrate risk information in preventive antiemetic strategies. Sufficient acute nausea and vomiting control are crucial to prevent delayed CIN.

Ultra Short Course Chemotherapy for Early-Stage Non-Hodgkin's Lymphoma in Children.

Early-stage non-Hodgkin’s lymphomas (ES-NHL) are associated with high survival rates. To minimize the risk of long-term sequelae, the duration and intensity of chemotherapy have been progressively reduced. Between 1988 and 2018, children with ES-NHL were treated at a single institute with two subsequent protocols. Protocol I consisted of a 7-week induction phase followed by a maintenance phase alternating 6-mercaptopurine plus MTX, a brief reinduction, and thioguanine plus cytosine arabinoside, for a total duration of 8 months. The subsequent protocol II (applied since 1997) was modified adding etoposide plus a further dose of HD-MTX and omitting maintenance in all histological subtypes except T-lymphoblastic lymphoma (T-LBL), for a total duration of 9 weeks. Intrathecal prophylaxis was not provided in either protocol. With a median follow-up of 98.4 months, the 5-year event-free survival (EFS) rates in protocol I (n = 21) and II (n = 25) were 76.2% and 96%, respectively, and the 5-year overall survival (OS) rates were 90.5% and 96%, respectively. None of the patients experienced disease progression or relapse within the central nervous system (CNS). Acute toxicity was manageable in both protocols, except for a case of presumed acute cardiotoxic death; no chronic sequelae were evident. Low-intensity chemotherapy for 9 weeks without intrathecal prophylaxis was sufficient for curing children with ES-NHL, without jeopardizing the excellent survival rate of this disease.

Prognosis of asymptomatic versus symptomatic metastatic breast cancer: a multicenter retrospective study

In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using tumor markers or imaging tests. We aimed to investigate differences in clinicopathological features, prognosis, and treatment between asymptomatic and symptomatic MBCs. Patients with MBC were retrospectively divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtype: luminal, human epidermal growth factor receptor 2 positive, and triple negative. Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts in the asymptomatic group tended to or had longer post-recurrence survival (PRS) than those in the symptomatic group. In contrast, all cohorts and TN patients in the asymptomatic group tended to have or had longer overall survival (OS) than those in the symptomatic group, although no significant difference was observed in the luminal and HER2 subtypes. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of PRS. Regarding the luminal subtype, the asymptomatic group had longer chemotherapy duration than the symptomatic group, with no significant difference in OS between the groups. Asymptomatic and symptomatic MBCs differ in terms of subtypes and prognosis, and whether they require different treatment strategies for each subtype warrants further investigation.

Does protracted chemotherapy have an influence on the clinical outcomes in advanced epithelial ovarian cancer?

In epithelial ovarian cancer, first-line adjuvant chemotherapy is necessary, and patients sometimes require protraction; however, there are only a few recent studies to show its influence. In this study, we investigated whether the protraction of the total period of first-line chemotherapy has a negative influence on the survival outcomes.Of the 101 patients we recruited from February 2011 to February 2021, 70 (69.3%) and 31 (30.7%) were classified into the not protracted and protracted groups, respectively. They underwent surgery and adjuvant chemotherapy for epithelial ovarian cancer. Protraction was defined as the overall duration of the first-line chemotherapy being more than 20 days longer than intended. Number of patients who underwent additional treatments such as bevacizumab or poly(adenosine diphosphate ribose) polymerase inhibitors or pembrolizumab was compared between both groups. Kaplan–Meier survival analysis and Cox regression analysis were used for survival outcomes.There was no significant difference for additional treatments. The progression-free survival (PFS) in the total follow-up period in the protracted group was significantly shorter than that in the not protracted group (P = .037); however, the difference in the overall survival between the 2 groups was not significant (P = .223). For the PFS, the hazard ratio of protraction was 1.646 in the univariate analysis (95% confidence interval, 1.020–2.658; P = .041).Excessive protraction of chemotherapy over 20 days or more can result in significantly shorter PFS within 5 years. A better therapeutic strategy is required for patients requiring protracted first-line chemotherapy in advanced epithelial ovarian cancer.

Geographic variation in attitudes regarding management of locally advanced pancreatic cancer

BackgroundRecent literature suggests wide variations exist in the international management of locally advanced pancreatic cancer. This study sought to evaluate how geography contributes to variations in management of locally advanced pancreatic cancer. MethodsAn electronic survey investigating preferences for the evaluation and management of locally advanced pancreatic cancer was distributed to an international cohort of pancreatic surgeons. Surgeons were classified according to geographic location of practice, and survey responses were compared across locations. ResultsA total of 153 eligible responses were received from 4 continents: North and South America (n = 94, 61.4%), Europe (n = 25, 16.3%), and Asia (n = 34, 22.2%). Preferences for the use and duration of neoadjuvant chemotherapy and radiotherapy varied widely. For example, participants in Asia commonly preferred 2 months of neoadjuvant chemotherapy (61.8%), whereas North and South American participants preferred 4 months (52.1%), and responses in Europe were mixed (P = .006). Participants in Asia were less likely to consider isolated liver or lung metastases contraindications to exploration and consequently had a greater propensity to consider exploration in a vignette of oligometastatic disease (56.7% vs North and South America: 25.6%, Europe: 43.5%; P = .007). ConclusionIn an international survey of pancreatic surgeons, attitudes regarding locally advanced pancreatic cancer and metastatic disease management varied widely across geographic locations. Better evidence is needed to define optimal management of locally advanced pancreatic cancer.