Cycle Of CTX Research Articles

Pediatric Liver Transplantation Secondary to Hepatoblastoma without the Use of a Kehr’s T Tube

Hepatoblastoma has a PRETEXT staging depending on the degree of hepatic involvement; stage IV is an indication for transplantation. At the same time, it has sought to reduce the occurrence of posttransplant complications by not using a Kehr’s T tube during the choledocho-choledochostomy, obtaining interesting results. A 16-month-old girl diagnosed with a PRETEXT IV hepatoblastoma, who received four courses of chemotherapy (CTX) with cisplatin plus doxorubicin, after she received a liver transplant and during surgery it was decided not to use a Kehr T-tube. She remained stable and had a favorable evolution, leaving on day 19 posttransplant. One month later, she received two cycles of adjuvant CTX with CAV scheme. Currently, she is free of disease. Even though the technique of choice is hepaticojejunostomy, it was decided to perform a choledocho-choledochostomy without a Kehr’s T tube, without the development of complications. Results in the literature show that the use of this technique prevents the appearance of complications in up to half of the cases, compared to when the tube is used.

Use of Stent in Choledochocholedochostomy for Pediatric Liver Transplantation Secondary to Hepatoblastoma: A Case Report

BACKGROUND: Hepatoblastoma is a malignant tumor with an insidious clinical presentation, however, it is characterized by an increase in abdominal circumference. In addition, there is PRETEXT staging based on the degree of liver involvement, which ranges from I to IV, of these, for stage IV the treatment of choice is liver transplantation. In addition, the use of stents in the the choledocho – choledochostomy has been tried to reduce post-transplant complications, with variable results. THE CASE: A 18-month-old female with a diagnosis of PRETEXT IV hepatoblastoma and a history of receiving 11 cycles of chemotherapy (CTX) with SIOPEL-3HR scheme, subsequently initiates protocol to receive liver transplantation for being an ideal candidate and PRETEXT IV staging, received from a related living donor. During surgery, it was decided to place a biodegradable stent to perform the choledocho – choledochostomy. She also had hemorrhagic shock grade IV secondary to blood loss, which was successfully resolved. In her first two days post-transplantation she presented adequate flows by Doppler ultrasound and liver enzymes with a downward trend, which remained with the same trend, and she was discharged on day 26 post-transplantation. The following month, she received a cycle of adjuvant CTX with SIOPEL-3HR scheme, without complications. One month later she presented cholestasis and jaundice, so the stent was removed. Currently free of disease, functional graft, and adequate psychomotor development. CONCLUSION: Although the use of a stent was intended to prevent complications such as biliary obstruction, since it is the most feared complication during liver transplantation, this was not the case of the patient, so it could be considered that it continues to be a controversial technique. Also, the use of chemotherapy after transplantation is important to be free of disease since clinical studies have shown an increase in patient survival.

Pediatric Liver Transplantation Secondary to Hepatoblastoma without the use of a Kehr’s T tube: A Case Report

BACKGROUND: Hepatoblastoma is a common primary malignant tumor in the pediatric population, it has a PRETEXT staging depending on the degree of hepatic involvement, in this stage III central and IV are indications for transplantation. At the same time, it has sought to reduce the occurrence of post-transplant complications by not using a Kehr’s T tube during the choledocho – choledochostomy, obtaining interesting results. THE CASE A 16-month-old woman diagnosed with PRETEXT IV hepatoblastoma, who received four cycles of chemotherapy (CTX) with cisplatin plus doxorubicin, adding two cycles of ICE, before her next cycle she was informed of the availability of a cadaveric liver graft, for this reason she received a liver transplant and during surgery it was decided not to use a Kehr’s T tube. She remained stable on her first post-transplant day. On her second day, a collection in the hepatic hilum was evidenced by control Doppler ultrasound (US), placing two Blake drains. The following four days she had a favorable evolution, being discharged to transplantation floor with a downward trend of liver enzymes, where she continued with the same trend and US Doppler with adequate flows, leaving on day 19 post-transplant. One month later, she received two cycles of adjuvant CTX with CAV scheme. Currently, graft is functional and free of disease. CONCLUSION: Liver transplantation is the treatment of choice, reaching a survival rate of over 80% at five years post-transplantation. Furthermore, even though the technique of choice is hepaticojejunostomy, it was decided to perform a choledocho – choledochostomy without a Kehr’s T tube, without the development of complications, which is consistent with results in the literature that show that the use of this technique prevents the appearance of complications in up to half of the cases, compared to when the tube is used. Also, adjuvant QT contributes to a better evolution and to obtaining a negative tumor marker, as was the case of the patient.

SAT219 Severe Isolated Hypocalcemia With Cetuximab & Irinotecan Chemotherapy

Abstract Disclosure: M. Thomas: None. N. Janakiram: None. J. Leary: None. K.E. Foster-Schubert: None. R.R. Narla: None. Background: Electrolyte disorders are commonly seen with chemotherapy (CTX) agents. Cetuximab is an epidermal growth factor receptor inhibitor and irinotecan is topoisomerase 1 inhibitor. Both agents have been associated with hypomagnesemia which can adversely lead to hypocalcemia (HC). Case: A 66-year-old woman with osteoporosis (last bisphosphonate use was 24 months ago), primary hyperparathyroidism status post parathyroidectomy in 2015 (R inferior and superior glands) and 2017 (L inferior gland) with recent diagnosis of metastatic adenocarcinoma of unknown primary who presented with nausea, tetany, leg cramps and found to have severe HC of corrected calcium (CCa) of 5.7, a week post-chemotherapy. On the day of her CTX, her CCa was 7.0, ionized calcium (iCal) of 1.7 with Magnesium (Mg) of 2.0; she received IV calcium (Ca), then underwent CTX. She was prescribed Ca supplements and reports adherence. She returned endorsing the above symptoms with positive Chvostek and Trousseau sign on exam. Labs were notable for CCa of 5.7, iCal of 1.6, Mg of 1.6, Phosphorus of 4.5, PTH 123 (ULN 65), 25-OH vitamin D of 28.6 and normal eGFR. She was hospitalized and received multiple infusions of IV Ca and CCa improved to 7.5. She was discharged on Ca carbonate 1000 mg TID, Mg oxide 420 mg BID and Vitamin D. Before her second cycle of CTX with same agents, she received IV Ca for CCa of 7.3. She remained on Ca and Mg supplements. One week later, she endorsed paresthesia, diarrhea and was admitted again for HC. She was initiated on calcitriol on this admission and 24-hour urine studies showed low Ca excretion and elevated fractional excretion of magnesium (FeMg). Her CCa was 8.0 and she was discharged on calcitriol 0.25 mg BID. Oncology discontinued this CTX regimen. Her HC resolved and calcitriol and Ca supplements were gradually weaned off. Discussion: After both rounds of cetuximab and irinotecan, our patient developed profound HC without hypomagnesemia. Cetuximab can cause occasional Mg wasting syndrome with inappropriate urinary excretion. However, she was started on Mg since her first hospitalization despite normal serum Mg levels. Interestingly, her 24-hour urine studies revealed FeMg of 6.5% suggestive of renal Mg wasting. In the literature, there is a case report of severe HC with irinotecan but they had speculated germline mutations in Ca metabolism genes. It remains unclear how these CTX agents impact Ca homeostasis. It is difficult to discern if the severe HC in our patient could be attributed to Mg wasting with normal Mg levels. It is evident that her HC was associated with the timing of her CTX regimen. Therapy for HC can be complex, involves short- and long-term interventions, and correction is critical. Serum Ca surveillance before and during CTX management of cancer patients may reveal more instances and provide insight into the exact mechanisms. Presentation: Saturday, June 17, 2023

Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Quality of life results of the randomized phase II AIO-NEONAX trial.

694 Background: Perioperative chemotherapy (CTX) in resectable pancreatic adenocarcinoma (rPDAC) is still not considered SoC and data regarding efficacy but also quality of life (QoL) are limited. NEONAX is a prospective, randomized phase II trial in patients with rPDAC with two independent experimental arms examining perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. The primary endpoint DFS at 18 mo. as well as DFS, OS and safety have already been reported. Here we present the QoL data of the NEONAX trial. Methods: QoL was evaluated by EORTC QLQ-C30, EORTC QLQ-PAN26 and HADS-D questionnaires at baseline, at the beginning of each CTX cycle (neoadj. and adj. in arm A, only adj. in arm B), after neoadj. treatment in arm A as well as prior and post resection and after 6 cycles of CTX. Results: Global health status score (GHS-score) (QLQ-C30) showed no difference between baseline (t1) and the timepoint after 6 cycles of CTX (t2) in the perioperative arm A (66.7/100 at both timepoints). Here patients experienced the lowest GHS-score pre- and postoperatively (50/100 in both cases). Adjuvant arm B showed a deterioration in the GHS-score of 12.5 points from timepoint 1 to 2 (62.5/100 to 50.0/100). Here the lowest GHS-score was observed within 4 weeks post-surgery (41.7/100). Physical function score (QLQ-C30) was decreased by 6.7 points (86.7/100 to 80/100) in perioperative arm A and by 26.7 points (86.7/100 to 60/100) in arm B between both timepoints. Role function (QLQ-C30) was reduced by 16.7 points (83.3/100 to 66.7/100) in arm A and by 33.3 points (83.3/100 to 50/100) in arm B between both timepoints. In the remaining subscales of the used questionnaires the two arms of the trial showed comparable median scores over the whole study period. The number of submitted questionnaires at each timepoint varied but was at large comparable in both arms. Conclusions: QoL was largely preserved in the perioperative as well as the adjuvant arm of the NEONAX trial. GHS-score was lower pre-and postoperatively in arm A. The lowest GHS-score was observed postoperatively in the adjuvant arm B. QoL was restored at the end of the treatment period in the perioperative arm A and remained slightly reduced in arm B suggesting that QoL is not substantially impaired by perioperative treatment in rPDAC. Clinical trial information: NCT02047513 . [Table: see text]

PET-directed combined modality therapy for gastroesophageal junction cancer: Results of the multicentre prospective MEMORI trial of the German Cancer Consortium (DKTK)

BackgroundPositron emission tomography (PET) may differentiate responding and non-responding tumours early in the treatment of locally advanced gastroesophageal junction adenocarcinomas. Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). MethodsPatients underwent baseline 18F-FDG PET followed by 1 cycle of CTX. PET was repeated at day 14–21 and responders (P-R), defined as ≥35% decrease in SUVmean from baseline, continued with CTX. P-NR switched to CRT (CROSS). Patients underwent surgery 4–6 weeks post-CTX/CRT. The primary objective was an improvement in R0 resection rates in P-NR above a proportion of 70%. ResultsIn total, 160 patients with resectable gastroesophageal junction adenocarcinomas were prospectively investigated by PET scanning. Eighty-five patients (53%) were excluded. Seventy-five eligible patients were enrolled in the study. Based on PET criteria, 50 (67.6%)/24 (32.4%) were P-R and P-NR, respectively. Resection was performed on 46 responders, including one patient who withdrew the ICF, and 22 non-responders (per-protocol population). R0 resection rates were 95.6% (43/45) for P-R and 86.4% (19/22) for P-NR. No treatment related deaths occurred. With a median follow-up time of 24.5 months, estimated 18 months DFS was 75.4%/64.2% for P-R/P-NR, respectively. The estimated 18 months OS was 95.5% for P-R and 68.2% for P-NR. ConclusionThe primary endpoint of the study to increase the R0 resection rate in metabolic NR was not met. PET response after induction CTX is prognostic for outcome with a prolonged OS and DFS in PET responders. Trial registrationNCT 2014-000860-16.

Depression trajectories among women undergoing chemotherapy.

e24144 Background: Depressive symptoms are common among women undergoing chemotherapy (CTX) for breast or gynecological cancer. Many studies have examined the prevalence of depressive symptoms (usually at the beginning or end of CTX). However, given that CTX unfolds over a number of cycles, there is a need to better understand patterns of change in depressive symptoms over the course of treatment, and to identify factors that may predispose individuals to worse symptom trajectories. The purpose of this study, among women who underwent CTX for breast or gynecological cancer, was to evaluate for interindividual differences in depressive symptoms over the course of two cycles of CTX, and to identify characteristics associated with both initial levels (i.e., at the beginning of the study) and trajectories of depressive symptoms. Methods: Patients undergoing CTX for breast (n = 530) or gynecologic (n = 233) cancer completed the Center for Epidemiological Studies-Depression (CES-D) questionnaire six times over two treatment cycles. Patient-reported measures were used to assess demographic, clinical, symptom, stress, and coping characteristics at enrollment. Using hierarchical linear modeling (HLM), we evaluated characteristics associated with initial levels and trajectories of depressive symptoms. Results: One demographic (marital status) and two clinical (number of comorbidities, functional status) characteristics predicted interindividual differences in initial levels of depressive symptoms. One demographic (education) and one clinical (MAX-2 score, a CTX toxicity metric) characteristic were associated with interindividual differences in depressive symptom trajectories. Several symptom characteristics predicted interindividual differences in initial levels (i.e., morning fatigue), trajectories (i.e., initial level of depression), or both initial levels and trajectories (i.e., sleep disturbance, attentional function) of depressive symptoms. Two stress-related variables (i.e., perceived stress, cancer-related distress) predicted interindividual differences in both initial levels and trajectories of depressive symptoms. Several coping variables predicted interindividual differences in initial levels (i.e., behavioral disengagement), trajectories (i.e., venting), or both initial levels and trajectories (i.e., self-blame) of depressive symptoms. Conclusions: The range of demographic, clinical, symptom, stress and coping characteristics associated with interindividual differences in depressive symptoms underscores the importance of evaluating risk and protective factors. These factors may serve as useful markers for both screening and intervention to address depressive symptoms during CTX.

Incidence, severity, and onset of oral mucositis in 5-FU based chemotherapy for gastrointestinal cancer.

77 Background: 5-fluorouracil has been used in treatment of gastrointestinal cancers for more than 40 years. Numerous toxicities of 5-FU are known. Little is known about the occurrence, natural course and causes of oral mucositis (OM) of 5-FU in GI tumors. There is little data on the additional toxicity of VEGF and EGFR antibodies together with 5-FU. We followed the occurrence, severity and localization of OM of 5-FU in consecutive patients as part of their cancer treatment. The primary aim of the study was to determine the severity, course and risk factors of OM up to the first six cycles of ctx. OM was evaluated by repeated inspections of the oral cavity and patient questionnaires. Methods: Pts who received 5-FU for the first time or who had not received ctx for at least 12 months. 64 consecutive pts were included in the observational study from March 2018 to March 2019. Out of 64 pts a total of 41 (28 m/13f) had complete documentations (inspections of the oral cavity and questionnaires) and were available for the evaluation. Results: Mean age 65 ys (range 42-83), 60% were treated for CRC, 22% esophageal/gastric cancer, and 18% other GI-cancers. 13 were non-smokers, 25 former smokers; 7 pts had daily alcohol consumption while 7 pts never consumed alcohol. 10/41 pts wore a dental prosthesis. The mean BMI was 26.5 (range 18.8-41.5). Initial very good/ good oral hygiene was given in 3/20 patients. 80% of the pts developed xerostomia after the first cycle, almost every patient needed support for symptoms due to oral problems during ctx. Of 41 pts, an OM could be documented in 38 pts. A total of 93% of the patients developed a mild course of the mucositis with grade 1-2. OM developed between the 2nd and 3rd cyle in the majority of pts. At the third cyle, only 8 pts had OM of grade 0, while 23 pts had grade 1 and 9 pts were grade 2. It was of note here that of these 9 pts with grade 2, 6 had grade 0 in the 2nd cycle. During cycle 5 and 6 only seven pts had a CTC score of 0, but no pat developed a CTC 3 or 4 OM. We could not document a connection between the occurrence of oral mucositis and the oral hygiene measures used, as no severe course of OM CTC Grad 3 or 4 could be detected. We could not find any relation to the type of 5-FU therapy (doublet, triplet +/- monoclonal antibodies). Conclusions: The incidence of oral mucositis with CTC score of 1 and 2 was 93%, but serious grade 3 and 4 mucositis rates were not observed. Xerostomia was observed in 80% after the first course of treatment. Symptomatic mucositis occurs early within 4 weeks after starting chemotherapy. Local measures appear suitable for symptom control of OM.

Institutional chart review on same-day pegfilgrastim administration in small cell lung cancer (SCLC) patients receiving myelotoxic chemotherapy.

71 Background: Pegfilgrastim administration is recommended at least 24 hours after the end of chemotherapy (CTX) treatment for prevention of chemotherapy-induced (febrile) neutropenia (CIN/FN). Published studies have found no differences in the risk of FN between same-day and next-day pegfilgrastim administrations in certain cancers. To evaluate the efficacy and safety of same-day compared to next-day pegfilgrastim administration in SCLC patients, we evaluated our own institutional data. Methods: Using ICD-9 and ICD-10 codes for SCLC, electronic health records were reviewed retrospectivey for the period 11/1/2013-8/31/2018 at the University of Arizona Cancer Center (UACC). Inclusion criteria were age 18 or older, biopsy confirmed SCLC diagnosis, treated at UACC, and pegfilgrastim administration on the same day as CTX. Outcomes collected in the first cycle and all cycles of CTX were: FN incidence, CIN grade 3/4, and treatment delay or hospitalizations due to CIN/FN. Results: Out of 1,181 patient records, 34 patients met inclusion criteria. The median age was 67.5 years, 23.5% of patients had stage 3 or 4 SCLC while 50% had 0-1 ECOG status. 44.1% of patients had a risk based on the type of CTX. Average baseline absolute neutrophil count was 5.55x109cells/L (SD=1.27x109cells/L). A total of 104 CTX cycles were given. Outcomes are summarized in the Table below. After the first cycle, the incidence rate of CIN grade 3/4 was 5.88%, but 0% for all other outcomes. Conclusions: After the first cycle, there were s of FN and no patients experienced treatment delays or hospitalizations related to CIN/FN; only two cases for CIN grade 3/4 were observed. Across all cycles, CIN grade 3/4 was observed in 17 cycles. In only two cycles, treatment was delayed or patient was hospitalized due to CIN/FN, not involving same patients. FN was observed in only 3/104 cycles. All observed rate were comparable or lower than known rates for next-day pegfilgrastim administration. Future studies including randomized trials should be further evaluated.[Table: see text]

An institutional evaluation of the safety and efficacy of same-day administration of pegfilgrastim in patients receiving chemotherapy for lung cancer.

e18591 Background: Pegfilgrastim is recommended to be administered 24 hours after myelosuppressive chemotherapy (CTX) as prophylaxis for chemotherapy-induced (febrile) neutropenia (CIN/FN). Recent studies have yielded equivocal data on same day versus next day administration of pegfilgrastim. There has been limited real world evidence addressing lung cancer (LC) patients and the use of same day pegfilgrastim. We evaluated our own institutional data on the safety of same day pegfilgrastim administration in LC patients. Methods: A retrospective chart review was performed by searching electronic health records using ICD-9 and ICD-10 codes corresponding with a lung cancer diagnosis between November 1, 2013 and August 31, 2018 at The University of Arizona Cancer Center (UACC). Patients included in the study were 18 years of age or older, diagnosed with biopsy-confirmed lung cancer, treated at UACC, and receiving chemotherapy and pegfilgrastim on the same day. The outcomes of interest included FN incidence after the first cycle and across all cycles of CTX, CIN grade 3/4 and CTX dose delays or hospitalizations due to CIN/FN after first cycle and across all cycles of CTX. Results: 1,181 patient records were reviewed and 114 patients met the inclusion criteria; 87 (76%) patients had non-small cell LC and 27 (24%) patients had small cell LC. The median age was 68 years, 52% of patients had cancer stage of 3 to 4, and 63% of patients had 0-1 ECOG status. The FN risk assessment was mild in 72% of patients. The mean (SD) of baseline absolute neutrophil count was 5.68 (3.09). In total 384 CTX cycles were received. The table shows the results of all intended outcomes. One patient experienced FN after the first cycle of CTX of irinotecan and 5 patients developed 6 FN episodes across all cycles; 2 patients were on carboplatin etoposide; 1 patient on cisplatin etoposide; 1 patient on vinorelbine and 1 patient was on pemetrexed and then on irinotecan CTX when the two FN episodes were developed. Conclusions: This study showing that same day administration of pegfilgrastim was as effective as next day administration in LC patients, without warranting any concerns for febrile neutropenia or delayed engraftment. Utilization of same day pegfilgrastim, in light of biosimilars and COVID, provides a unique opportunity for cancer care without concerns for FN as stated in previous studies.[Table: see text]

Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial

Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population. This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [≥5 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18-59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0-3, or aged 60-65 years with ECOG 0-2. After an optional prephase with vincristine and steroids (intravenous vincristine 1·4 mg/m2 on day 1, oral prednisone 100 mg [total dose] on days 1-5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m2 on day 1; intravenous doxorubicin 50 mg/m2, vincristine 1·4 mg/m2, and cyclophosphamide 750 mg/m2 on day 2; oral prednisone 100 mg/m2 on day 2-6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m2 on day 1, intravenous rituximab 375 mg/m2 on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m2 every 12 h on days 1-3, intravenous rituximab 375 mg/m2 on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100 × 109 cells per L or 10 mg per day for platelets 60-100 × 109 cells per L, days 1-21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009-012807-25) and ClinicalTrials.gov (NCT02354313). Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51-62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24-50), 3-year progression-free survival was 80% (95% CI 70-87) in the lenalidomide group versus 64% (53-73) in the observation group (log-rank test p=0·012; hazard ratio 0·51, 95% CI 0·30-0·87). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3-4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p<0·0001). 29 (31%) of 93 patients in the lenalidomide group and eight (8%) of 101 patients in the observation group had grade 3-4 non-haematological adverse events (p<0·0001), of which infections were the most common.Serious adverse events were reported in 22 (24%) of 93 patients in the lenalidomide group and five (5%) of 101 patients in the observation group. Pneumonia and other infections were the most common serious adverse events. Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma. Fondazione Italiana Linfomi and Celgene.

Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin’s disease: results of the Groupe d’études des Lymphomes de l’Adulte H89 trial

AbstractThe treatment of advanced Hodgkin's disease (HD) with chemotherapy (CTx) alone or combined modality treatments has been controversial. In 1989, we designed a randomized study to compare 2 cycles of CTx to (sub)total nodal irradiation (RTx) as consolidation treatments for patients with stage IIIB/IV HD in complete remission (CR) or good partial response after 6 cycles of CTx. A total of 559 patients were randomized to receive 6 cycles of MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine) hybrid (n = 266) or ABVPP (n = 267). After induction treatment, 418 patients could be evaluated for the consolidation phase. With a median follow-up of 48 months, the 5-year disease-free survival estimates were 80% for 8 cycles of MOPP/ABV, 82% for 6 cycles of MOPP/ABV plus RTx, 68% for 8 cycles of ABVPP, and 75% for 6 cycles of ABVPP plus RTx (P = .01). The 5-year disease-free survival estimates did not differ between CTx and RTx, 74% and 79%, respectively (P = .07). After MOPP/ABV, the 5-year overall survival estimates did not differ between CTx and RTx, 85% and 88%, respectively (P = .2). After ABVPP, the 5-year survival estimates were 94% for CTx and 78% for RTx (P = .002). These results showed that RTx was not superior to CTx consolidation after doxorubicin-induced CR for patients with advanced HD. Because of the uncertainty of obtaining a prolonged second remission for patients relapsing after CTx and RTx and the possible long-term effects of RTx, we prefer 8 cycles of CTx as standard treatment when a CR has been achieved after 6 cycles.

Oncoxin-Viusid® may improve quality of life and survival in patients with hormone-refractory prostate cancer undergoing onco-specific treatments.

The aim of the present study was to identify the efficacy and safety of Oncoxin-Viusid (OV) as a supportive treatment for patients with prostate cancer (PCA). A prospective, non-randomised, open-label phase II clinical trial, including 25 patients with hormone-refractory PCA (HRPC) was conducted at the Hospital Universitario General Calixto García (Havana, Cuba) between June 2017 and March 2018. Each of the patients received chemotherapy (CTX) and/or radiotherapy (RT) and OV treatment. Patients had a mean age of 73 years, clinical stage IV cancer and a high risk of relapse. Six cycles of CTX were completed by 80% of the patients, adverse reactions decreased and no weight loss was observed. Among the 25 patients, 5 were lost to follow-up and 4 died of disease progression. A total of 16 of these patients survived, of which 15 had an improved quality of life and 10 responded to treatment, with a significant reduction in pain and prostate symptoms and ≥50% reduction in baseline PSA. The progression-free survival (PFS) rate was 59% and the overall survival (OS) rate 64% at 1 year after treatment began. The OV nutritional supplement was effective, leading to a significant improvement in the patients' quality of life, good nutritional status and greater treatment tolerance. A clinical and humoral response was observed, with high survival rates and a delayed appearance of signs of disease progression. The present study was registered in ClinicalTrials.gov PRS with ID #NCT03543670.

Perturbations in Endocytotic and Apoptotic Pathways Are Associated With Chemotherapy-Induced Nausea.

While vomiting is well controlled with current antiemetic regimens, unrelieved chemotherapy-induced nausea (CIN) is a significant clinical problem. Perturbations in endocytotic and apoptotic pathways in the gut can influence the functioning of the microbiome-gut-brain-axis and the occurrence of gastrointestinal (GI) symptoms. However, limited information is available on the mechanisms that underlie unrelieved CIN. The purpose of this study was to evaluate for perturbed biological pathways associated with endocytosis and apoptosis in oncology patients who did (n = 353) and did not (n = 275) report CIN prior to their second or third cycle of chemotherapy (CTX). Oncology patients (n = 735) completed study questionnaires in the week prior to their second or third cycle of CTX. CIN occurrence was evaluated using the Memorial Symptom Assessment Scale. Pathway impact analyses (PIA) were performed in 2 independent samples using RNA-sequencing (sample 1, n = 334) and microarray (sample 2, n = 294) methodologies. Fisher's combined probability method was used to identify signaling pathways related to endocytotic and apoptotic mechanisms that were significantly perturbed between the 2 nausea groups across both samples. CIN was reported by 63.6% of the patients in sample 1 and 48.9% of the patients in sample 2. Across the 2 samples, PIA identified 4 perturbed pathways that are involved in endocytosis (i.e., endocytosis, regulation of actin cytoskeleton) and apoptosis (i.e., apoptosis, PI3K/Akt signaling). Our findings suggest that CTX-induced inflammation of the GI mucosa, that results in the initiation of endocytotic and apoptotic processes in the gut, is associated with the occurrence of CIN.

Stable Symptom Clusters and Evolving Symptom Networks in Relation to Chemotherapy Cycles

ContextThe existence of stable symptom clusters with variations or changes in cluster membership and the merging of symptom clusters over time urge us to investigate how symptom relationships change over time. ObjectivesTo identify stable symptom clusters and understand networks among symptoms using longitudinal data. MethodsSecondary data analysis was conducted using data from a nonblinded randomized clinical trial, which evaluated the effect and feasibility of the developed cancer symptom management system. For the present study, data from all participants of the original trial were analyzed (N = 249). The severity of 20 symptoms was measured before the start of chemotherapy (CTx) and during the initial four cycles of CTx. Symptom clusters were identified using principal component and hierarchical cluster analyses, and network analysis was used to explore the relationships among symptoms. ResultsThree common symptom clusters were identified. The first cluster consisted of anxiety, depression, sleep disturbance, pain, and dyspnea. Fatigue, difficulty concentrating, and drowsiness formed a second stable cluster throughout the CTx cycles. The third cluster comprised loss of appetite, taste change, nausea, and vomiting. In terms of the symptom networks, close relationships were recognized, irrespective of symptom severity level, between anxiety and depression, fatigue and drowsiness, and loss of appetite and taste change. Fatigue was the most central symptom with the highest strength. Edge thickening after starting CTx demonstrated evolving symptom networks in relation to CTx cycles. ConclusionStable symptom clusters and evolving networks were identified. The most central symptom was fatigue; however, the paucity of studies that investigated symptom networks and central symptoms calls for further investigations on these phenomena. Identification of central symptoms and underlying mechanisms will guide efficient symptom management. Future studies will need to focus on developing comprehensive interventions for managing symptom clusters or targeting central symptoms.

A phase II trial of pembrolizumab in combination with cisplatin or carboplatin and etoposide in chemotherapy naive patients with metastatic or unresectable high-grade gastroenteropanncreatic or lung neuroendocrine carcinoma.

TPS635 Background: Combination chemotherapy (CTx) is the mainstay of treatment for patients with advanced high-grade gastroenteropancreatic neuroendocrine carcinoma (GEPNECs) and large cell neuroendocrine carcinomas (LCNECs) of the lung. Pembrolizumab (PEM) is a humanized antibody to the programmed cell death receptor (PD-1), which blocks the interaction with its cognate ligands, PD-L1 and PD-L2. PEM blocks the protective mechanism of cancer cells and allows the immune system to destroy them. Combination Ctx and immunotherapy has shown efficacy in other malignancies including small cell lung cancer. The purpose of this study is to test the efficacy, safety, and tolerability of combination CTx with PEM in patients with high-grade GEPNEC or LCNEC of the lung who are CTx naïve. Methods: This is an open label, phase II, single institution, multi-site trial using PEM in combination with either cisplatin or carboplatin and etoposide in patients with high grade GEPNECs or LCNEC of the lung who are CTx naïve. Patients with a histologic diagnosis of a GEPNECs with a Ki-67 of 55% or higher or a LCNEC of the lung will be eligible. Patients must be metastatic or unresectable; chemotherapy naïve; have at least one measurable lesion per RECIST 1.1, have an ECOG performance score of 0-1; and have a predicted life expectancy &gt; 3 months. Approximately 36 GEPNEC and 6 LCNEC of the lung patients will be enrolled. Patients will receive PEM 200mg IV in combination with cisplatin 80 mg/m2 or carboplatin AUC 6 on day 1 and etoposide 100mg/m2 on days 1-3 of a 21-day cycle. Tumor response will be assessed by CT scan every 6 weeks using RECIST 1.1. Those patients who have responsive or stable disease after 4-6 cycles of platinum-based CTx will move to maintenance PEM every 3 weeks for up to 2 years. The primary endpoint will be progression free survival. Results: This study is open to enrollment. Clinical trial information: NCT03901378.

Efficacy of Irinotecan as Third-line Chemotherapy for Unresectable or Recurrent Gastric Cancer.

To evaluate the efficacy and safety of third-line chemotherapy (CTx) for patients with unresectable or recurrent gastric cancer (GC) refractory to S-1 with or without platinum and taxanes. We retrospectively analyzed clinicopathological and survival data of 26 patients who underwent third-line CTx. Irinotecan therapy (odds ratio=0.12, 95% confidence interval=0.02-0.38; p<0.01) and ≥2 cycles of third-line CTx (odds ratio=0.01, 95% confidence intervaI=0.01-0.11; p<0.01) were independent predictors of longer progression-free survival in multivariate Cox regression analysis. In 18 patients (69%) receiving irinotecan, the overall response rate was 11%, and the disease control rate was 44%. Median progression-free and overall survival were 3.5 and 11.3 months, respectively. Ten patients (56%) had grade 3-4 toxicities, which were managed. Irinotecan therapy may become optimal and tolerated in the third-line setting to prolong progression-free survival by increasing the number of treatment cycles.

Neuropsychological Symptoms and Intrusive Thoughts Are Associated With Worse Trajectories of Chemotherapy-Induced Nausea

ContextAlthough chemotherapy-induced vomiting is well controlled with evidence-based antiemetic regimens, chemotherapy-induced nausea (CIN) remains a significant clinical problem. ObjectivesStudy purposes, in a sample of outpatients with breast, gastrointestinal, gynecological, or lung cancer who received two cycles of chemotherapy (CTX, n = 1251), were to evaluate for interindividual differences in the severity of CIN and to determine which demographic, clinical, symptom, and stress characteristics are associated with higher initial levels as well as with the trajectories of CIN. MethodsPatients were recruited during their first or second cycle of CTX. Patients completed self-report questionnaires a total of six times over two cycles of CTX. Hierarchical linear modeling was used to evaluate for interindividual differences in and characteristics associated with the severity of CIN. ResultsAcross the two cycles of CTX, higher levels of sleep disturbance, depression, and morning fatigue, as well as higher levels of intrusive thoughts, were associated with higher initial levels of CIN. In addition, lower functional status scores and shorter cycle lengths were associated with higher initial levels of CIN, and younger age and higher emetogenicity of the CTX regimen were associated with both higher initial levels as well as worse trajectories of CIN severity. ConclusionThese findings suggest that common symptoms associated with cancer and its treatment are associated with increased severity of CIN. Targeted interventions for these symptoms may reduce the burden of unrelieved CIN.

Gastrointestinal symptoms are associated with trajectories of chemotherapy-induced nausea

Between 19 and 58% of oncology patients experience chemotherapy-induced nausea (CIN). In a sample of outpatients with breast, gastrointestinal (GI), gynecological, and lung cancer, the study purposes were to evaluate for inter-individual differences in the severity of CIN over two cycles of chemotherapy (CTX) and to determine which demographic and clinical characteristics and GI symptoms were associated with higher initial levels as well as with the trajectories of CIN severity. Patients completed study questionnaires at six time points over two cycles of CTX. These questionnaires provided information on demographic and clinical characteristics, as well as the occurrence of twelve GI symptoms. Hierarchical linear modeling based on full maximum likelihood estimation was performed. Of the 1251 patients, 47.2% reported CIN. Across two cycles of CTX, lower functional status scores and higher levels of comorbidity were associated with higher initial levels of CIN. Younger age and emetogenicity of the CTX regimen were associated with higher initial levels as well as worse trajectories of CIN. The occurrence of five GI symptoms (i.e., vomiting, lack of appetite, constipation, feeling bloated, and difficulty swallowing) was associated with higher initial levels of CIN. The occurrence of mouth sores was associated with higher initial levels as well as with worst trajectories of CIN. This study is the first to identify distinct demographic, clinical, and GI symptom characteristics associated with CIN severity. These findings suggest that the etiology of CIN is complex and may warrant interventions beyond standard antiemetics.

Stability of Symptom Clusters in Patients With Gastrointestinal Cancers Receiving Chemotherapy

ContextLimited evidence suggests that patients with gastrointestinal (GI) cancers receiving chemotherapy (CTX) experience an average of 13 co-occurring symptoms. An alternative to counting symptoms is to evaluate for symptom clusters. ObjectivesIn a sample of patients with GI cancers receiving CTX (n = 399), we evaluated the occurrence, severity, and distress of 38 symptoms in the week before patients' second or third cycle of CTX (Time 1 [T1]), approximately one week after CTX (Time 2 [T2]), and approximately two weeks after CTX (Time 3 [T3]); evaluated for differences in the number and types of symptom clusters at each of these three assessments using ratings of occurrence, severity, and distress; and evaluated for changes in symptom clusters over time. MethodsModified version of the Memorial Symptom Assessment Scale collected data on 38 common symptoms. Exploratory factor analyses were used to create the symptom clusters. ResultsFive distinct symptom clusters were identified across the three symptom dimensions and the three assessments (i.e., psychological, CTX-related, weight change, GI, and epithelial). Psychological, CTX-related, and weight change clusters were relatively stable across all three symptom dimensions and time. Across all three symptom dimensions, GI cluster was identified only at T1 and epithelial cluster was identified at T2 and T3. ConclusionThe number and types of symptom clusters appear to be relatively stable over time and across the symptom dimensions. Ongoing assessment and management of these clusters is warranted across the entire course of CTX. The underlying mechanism for these clusters warrants investigation.