Mild obesity does not affect perinatal outcome in gestational carrier cycles.

STUDY QUESTION: Does BMI of gestational carriers (GCs) affect perinatal outcomes after embryo transfer? SUMMARY ANSWER: Overweight and class I obesity in GCs does not affect the rate of good perinatal outcomes. WHAT IS KNOWN ALREADY: The use of GCs is increasing, but uniform guidance regarding optimal BMI for GCs is lacking. Women with obesity who conceive without fertility treatment or through autologous or donor in vitro fertilization are at higher risk of adverse maternal and fetal outcomes, but data on obesity in GCs are very limited. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of 1121 GC cycles from January 2015 to December 2020 at US Fertility, the largest national partnership of fertility practices in the USA. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All GC cycles performed at a large network of fertility practices were reviewed. Same-sex partners undergoing co-IVF were excluded. The primary outcome was good perinatal outcome from the first embryo transfer, defined as a singleton live birth at ≥37 weeks of gestation with birth weight between 2500 and 4000 g. Secondary outcome measures included frequencies of live birth, clinical pregnancy, miscarriage, full-term birth, low birth weight, large for gestational age, and cesarean delivery. A generalized linear model (log-binomial) was used for each to compare outcomes across BMI groups using normal BMI (20-24.9 kg/m2) as the reference group. Risk ratios and 95% CIs were estimated for each category group relative to normal BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1121 cycles in which GCs underwent first embryo transfer, of which 263 (23.5%) were in GCs with BMI >30. Demographics and reproductive history for GCs did not differ by BMI groups. The age of intended parents, use of frozen eggs, and fresh embryo transfers were higher with increasing BMI group. There were no statistically significant associations between BMI and good perinatal outcomes, live birth, clinical pregnancy, biochemical, spontaneous abortion, or low birth weight. However, among live births, higher BMI was significantly associated with birth by cesarean (P = 0.015) and large for gestational age infants (P = 0.023). LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study, and there may be unmeasured confounders. The number of patients with BMI <20 or ≥35 was small, limiting the power for these groups. We were not able to assess all maternal and fetal outcomes. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we did not identify any significant impact of BMI on the chances of having a good perinatal outcome. Prior research studies have been inconsistent and this is the largest study to date. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this work. The authors do not have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial.

Background: High-dose therapy and autologous stem cell transplantation (ASCT) is often considered for older patients (age >60 years) with relapsed/refractory aggressive lymphomas. Although registry data support the safety and potential efficacy of this approach, there are no prospective trials evaluating outcomes of ASCT in older patients. We evaluated the result of second-line chemotherapy and ASCT in older versus younger patients in the CCTG randomized LY.12 trial. Patients and methods: From August 2003 to November 2011, 619 patients with relapsed/refractory aggressive lymphoma were randomized to gemcitabine, dexamethasone, cisplatin (GDP) or dexamethasone, cytarabine, cisplatin (DHAP); 177 patients (28.6%) enrolled were >60.0 years of age (range, 60-74) and 442 were ≤60.0 years of age. After two to three cycles, responding patients proceeded to ASCT. Intention-to-treat analysis was used to compare response rate, transplantation rate, event-free survival (EFS) and overall survival (OS) between patients aged ≤60.0 and >60.0 years. Results: Patient characteristics were comparable between the two cohorts, except a larger proportion of older patients had high International Prognostic Index risk scores. Response to salvage therapy was 48.6% for patients aged >60.0 versus 43.0% for those aged ≤60.0 (P = 0.21). Transplantation rates were also similar: 50.3% versus 49.8% (P = 0.87) for older versus younger patients. Rates of febrile neutropenia and adverse events requiring hospitalization were comparable for older and younger patients (30.5% versus 22.9% and 37.9% versus 32.1%, respectively). With a median follow-up of 53 months, there was no difference in 4-year OS (36% and 40% for patients aged >60.0 and ≤60.0 years, P = 0.42), or 4-year EFS (20% versus 28%, P = 0.43). Mortality from salvage therapy was 8/174 (4.60%) and 5/436 (1.15%), and 100-day mortality post-ASCT was 7/88 (8.06%) and 4/219 (1.85%). Conclusion: This subgroup analysis suggests that older patients derive similar benefit from salvage therapy and ASCT to younger patients, with acceptable toxicity. ClinicalTrials.gov Identifier: NCT00078949.

A multi-method review of home-based chemotherapy.

This study summarises research- and practice-based evidence on home-based chemotherapy, and explores existing delivery models. A three-pronged investigation was conducted consisting of a literature review and synthesis of 54 papers, a review of seven home-based chemotherapy programmes spanning four countries, and two case studies within the Canadian province of Ontario. The results support the provision of home-based chemotherapy as a safe and patient-centred alternative to hospital- and outpatient-based service. This paper consolidates information on home-based chemotherapy programmes including services and drugs offered, patient eligibility criteria, patient views and experiences, delivery structures and processes, and common challenges. Fourteen recommendations are also provided for improving the delivery of chemotherapy in patients' homes by prioritising patient-centredness, provider training and teamwork, safety and quality of care, and programme management. The results of this study can be used to inform the development of an evidence-informed model for the delivery of chemotherapy and related care, such as symptom management, in patients' homes.

The relationship of multifocality and tumor burden with various tumor characteristics and survival in early breast cancer.

The presence of multifocality and the aggregate tumor size were retrospectively analysed in a database of 1071 operated breast cancers. Around a quarter of all these cancers involved multiple foci, while a tenth of the total demonstrated more than one invasive focus. Although the multifocal cancers were smaller and more often screen-detected than the unifocal cancers, their aggregate tumor size was larger, and they more frequently displayed casting-type calcifications in the mammogram and HER2 positivity. Lobular histology favoured larger tumor burden. The invasive multifocal cancers were more commonly lymph node-positive than the other tumors. In a subgroup of 584 patients with a median follow-up time of 5 years, the larger size of the invasive tumor, the presence of LVI or lymph node involvement, HER2 positivity and triple negativity were associated with a poorer RFS and OS, while the outcome of screen-detected tumors was superior to that of non-screen-detected or interval cancers. A large tumor size, lymph node positivity and HER2 positive or triple negative phenotypes were independent determinants of a poorer survival rate.

Is axillary lymph node dissection necessary for positive preoperative aspiration cytology lymph node results?

INTRODUCTION: Based on international guidelines, axillary lymph node dissection (ALND) is recommended in cases of breast cancer if preoperative examinations confirm axillary metastasis. We examined which set of preoperative parameters might render ALND unnecessary. PATIENTS AND METHODS: Preoperative examinations (axillary ultrasound and aspiration cytology) confirmed axillary metastasis in 190 cases out of 2671 patients with breast cancer; primary ALN dissection was performed on these patients with or without prior neoadjuvant therapy. The clinicopathological results were analysed to determine which parameter might predict the presence of no more than 2 or 3 metastatic ALNs. RESULTS: The final histological examination confirmed 1-3 metastatic lymph nodes in ALND samples in 116 cases and over 3 metastatic lymph nodes in 74 cases. For patients receiving neoadjuvant therapy (59 out of the 190 cases), if the size of the primary tumour was 2 cm or smaller and/or the metastatic ALN was 15 mm or smaller, then the patient was likely to have no more than 3 positive ALNs (stage N0-1 disease) (p < 0.001). If the patient did not receive neoadjuvant therapy, stage N2 or N3 disease was very likely. No correlation was found between other clinicopathological characteristics of the tumour and involvement of the ALNs. CONCLUSION: Axillary lymph node dissection is not necessary for selected breast cancer patients with axillary metastasis receiving neoadjuvant therapy. In these cases, sentinel lymph node biopsy with or without radiation therapy and close follow-up may serve as adequate therapy.

Is intraoperative touch imprint cytology indicated in the surgical treatment of early breast cancers?

INTRODUCTION: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results. METHODS: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 µm; impression smears were evaluated after being stained with hematoxylin eosin. RESULTS: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%. CONCLUSIONS: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer.

Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To assess whether prechemotherapy health-related quality-of-life (HQL) variables are associated with postchemotherapy nausea and vomiting (PCNV), and to determine their relationship to patient and treatment variables. PATIENTS AND METHODS: Eight hundred thirty-two chemotherapy-naive patients scheduled to receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist with or without dexamethasone for moderately or highly emetogenic chemotherapy were enrolled. HQL was measured by the self-report European Organization for Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ-C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as other patient, disease, and treatment variables were compared in the groups of patients who had PCNV and those who did not have PCNV. All variables were assessed initially in a univariate analysis and then together in a multivariate analysis using step-wise logistic regression. The final model generated by the multivariate analyses was used in a risk factor analysis to predict PCNV. RESULTS: Univariate analyses identified 10 HQL variables and five patient and treatment characteristics that were associated with PCNV. In the multivariate analysis, the variables remaining in the final model included low social functioning, prechemotherapy nausea, female gender, highly emetogenic chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or without dexamethasone) after chemotherapy. A history of low alcohol use was also associated with PCV, whereas increased fatigue and lower performance status were associated with PCN. In the risk factor analysis, the incidence of PCV increased from 20% in those having no risk factors to 76% in those having any four of the six risk factors. CONCLUSION: Several pretreatment HQL, patient, and treatment characteristics are associated with the occurrence of PCNV. Patients about to receive moderately or highly emetogenic chemotherapy should be screened for these factors and additional measures, such as behavior modification and modification of antiemetic therapy, should be considered in attempts to improve the control of PCNV.

Effect of schedule and maintenance on the antiemetic efficacy of ondansetron combined with dexamethasone in acute and delayed nausea and emesis in patients receiving moderately emetogenic chemotherapy: a phase III trial by the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: This study examines whether the schedule of ondansetron significantly influences its antiemetic efficacy in the first 24 hours after chemotherapy, whether the administration of oral ondansetron after 24 hours is effective in preventing delayed emesis, and whether the efficacy of ondansetron is preserved over multiple courses of moderately emetogenic chemotherapy. PATIENTS AND METHODS: A multicenter double-blind study randomized 302 cancer patients to one of three treatment arms. Arm A received dexamethasone 10 mg intravenously (i.v.) plus ondansetron (Zofran; Glaxo Canada Inc, Toronto, Canada) 8 mg i.v. prechemotherapy plus ondansetron 8 mg orally every 12 hours postchemotherapy for nine doses. Arm B received dexamethasone 10 mg i.v. plus ondansetron 16 mg i.v. prechemotherapy plus placebo orally postchemotherapy in the same schedule as arm A. Arm C received dexamethasone 10 mg i.v. plus ondansetron 8 mg prechemotherapy plus ondansetron 8 mg orally postchemotherapy for one dose followed by placebo orally every 12 hours for eight more doses. Response was assessed by the number of reported episodes of vomiting and by severity of nausea measured on a visual analog scale (VAS). RESULTS: The two schedules of ondansetron used in the first 24 hours were no different in their antiemetic efficacy, with similar rates for complete responses (76.7% v 72.0%, P = .472), complete plus major responses (90.2% v 82.0%, P = .135), and severity of nausea (P = .348). Oral ondansetron after 24 hours was more effective than placebo in preventing delayed nausea and emesis, with superior rates of complete responses (59.6% v 42.1%, P = .012 by one-sided test), complete plus major responses (80.9% v 66.3%, P = .018 by one-sided test), and less severe nausea (9.2 mm v 18.6 mm on a 100-mm VAS, P = .002). The efficacy of ondansetron was maintained over subsequent courses of chemotherapy. CONCLUSION: The schedule of ondansetron in the first 24 hours does not influence its efficacy. The use of oral maintenance ondansetron is effective in preventing delayed maintenance ondansetron is effective in preventing delayed nausea and emesis after moderately emetogenic chemotherapy.

A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis. An NCI Canada Clinical Trials Group Phase III Trial.

151 patients (149 evaluable) receiving their first course of chemotherapy containing cisplatin in a dose of at least 50 mg/m2 were randomised to receive either a single dose of intravenous granisetron 80 micrograms/kg or intravenous metoclopramide 2 mg/kg every 2 h for five doses plus a single dose of dexamethasone 10 mg and diphenhydramine. After 24 h, there was no significant difference between groups with respect to nausea or vomiting: in the granisetron group 46% of patients had no emesis, versus 44% of the standard group. Granisetron is an antiemetic agent with efficacy similar to that of high-dose metoclopramide plus dexamethasone.

A clinical and pharmacological study of 5-fluorouracil, leucovorin and interferon alfa in advanced colorectal cancer.

Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standard treatment approach in patients with metastatic colorectal cancer. Modulation of FUra with interferon alfa has also shown some promise. Laboratory data have demonstrated increased cytotoxicity when FUra is combined with both LV and interferon. The current study examined the effects of double modulation of FUra using LV and interferon. Patients with measurable advanced colorectal cancer received bolus FUra 375 mg/m2 plus LV 20 mg/m2 daily for 5 days, repeated every 28 days. Recombinant human interferon alfa-2a, 3 million IU/m2 subcutaneously, was given daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% CI 12.0-40.0%). Overall, 70% of patients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P < 0.0001). Improvements in tumor-related symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressive changes in FUra metabolism from interferon usage.

Combined results of two phase II studies of Taxol (paclitaxel) in patients with relapsed or refractory lymphomas.

This study was performed to determine the clinical activity and safety of paclitaxel in the treatment of patients with refractory or relapsing aggressive Non-Hodgkin's lymphoma (NHL). Between May 3, 1994 and February 16, 1996, 39 patients with refractory or relapsing NHL consented to be enrolled in two, multicenter, open-labelled studies to evaluate the efficacy, safety, time to progression and overall survival of paclitaxel given at a dose of 175 mg/m2 by a 3-hour IV infusion every three weeks without G-CSF use. Data from the two studies is combined. One patient, although registered, did not receive treatment. Of the remaining 38 patients, 17 men and 21 women aged 26-82 years (median 60) were given 104 courses of paclitaxel [median 2 (range 1-6)]. Seventeen patients had stage IV, 7 stage III, 8 stage II, 5 stage 1 and 1 unknown stage of disease. Histologic grades included 1 low, 33 intermediate, and 4 high. Three patients had bone marrow involvement. Median time from diagnosis to study entry was 19 months (1-160). The median number of previous chemotherapy regimens was 2 (range 1-6). Three of the 35 (8.6%) patients evaluable for response had partial remission (PR) of their disease for 1-7 months (median 2) and 11/35 (31.4%) stable disease (SD) for 1 to 19 months (median 3). All three responders and 3 of the 11 SD patients had received paclitaxel after relapsing from a CR. At analysis, nine of the 38 patients were alive. Median duration of follow up at analysis was 6 months (3 days-29 months). The estimated survival rates for all patients at 1 and 2 years are 34% and 27%, respectively (Kaplan-Meier) from the start of paclitaxel treatment. The median survival time was 5.4 months (3 days to 28+ months). Febrile neutropenia occurred in two patients. Seven (18%) patients developed a neutrophil nadir of < 0.5 x 10(9)/L and 2 (5%) patients developed a platelet nadir of < 50 x 10(9)/L. Six patients received blood transfusions. Non-hematologic toxicity was generally mild to moderate with all patients experiencing some toxicity. Twenty-seven patients experienced grade III toxicity including: alopecia (n = 19), pain (n = 9), fatigue (n = 5), nausea/vomiting (n = 3), diarrhoea (n = 2), pulmonary/shortness of breath (n = 2), anorexia (n = 1) and fluctuating levels of consciousness and somnolence (n = 1). Two patients experienced grade IV toxicity (infection, peripheral neuropathy, pain). No patient discontinued paclitaxel for a severe hypersensitivity reaction. In summary, administered as a 3-hour infusion, paclitaxel 175 mg/m2 results in mild myelotoxicity but minimal antitumor activity in patients with refractory NHL.

Parenchymal patterns of the breast defined by real time ultrasound.

The association of mammographic parenchymal patterns of the breast with breast cancer risk has been studied extensively but there is little information about the distribution of different patterns in populations at different risks for breast cancer. Such information could be obtained if a risk-free method of breast examination were available that could be applied to the general population. We have evaluated real time ultrasound for this application by comparing the parenchymal pattern as assessed by mammography with the extent of echogenicity in the breast on ultrasound examination in 102 subjects. Subjects were examined by both methods, the mammographic and ultrasound images independently classified, and the proportion of the breast occupied by radiological density or ductal prominence compared with the extent of echogenic areas on ultrasound. These two methods of classifying mammographic parenchymal patterns were found to be strongly correlated. Real time ultrasound may therefore be useful in the epidemiological study of mammographic pattern and breast cancer risk.

Ultrasonographically defined parenchymal patterns of the breast: relationship to mammographic patterns and other risk factors for breast cancer.

We have used ultrasound of the breast to define four parenchymal patterns in which increasing proportions of the breast are replaced by densely echogenic tissue. A series of 452 symptomatic women examined by both ultrasound and conventional X-ray mammography was reviewed to determine whether these ultrasonographic images could predict the breast parenchymal pattern defined mammographically. A very strong correlation was demonstrated between the breast pattern on ultrasound and the volume of the breast replaced by either dysplasia (Kendall's tau-b = 0.731 +/- 0.026, p less than 0.0001) or ductal prominence (Kendall's tau-b = 0.641 +/- 0.049, p less than 0.0001). This was seen both on initial reporting and on a blind re-reading of a random sample of 100 cases. The strength of correlation was similar for subgroups defined by family history of breast cancer, age, menopausal status, and history of benign breast disease, and the breast parenchymal pattern assessed by mammography or ultrasound showed similar associations with these variables. Ultrasonographic parenchymal patterns of the breast can predict the tissue patterns defined mammographically and may therefore be useful as a marker of breast cancer risk.

A phase II study of 5-fluorouracil, leucovorin and interferon-alpha in advanced pancreatic cancer.

Increased activity against colorectal cancer by 5-fluorouracil (5-Fu) modulation with leucovorin (LV) and/or interferon (IFN) has been reported. In this study 22 patients with measurable advanced pancreatic cancer received 5-Fu 375 mg/m2 and LV 20 mg/m2 by i.v. bolus daily x 5 every 28 days plus IFN-alpha 3 million units/m2 s.c. There were three out of 21 (14%) responses lasting from 4 to 8 months. Sixteen patients (73%) had one or more episodes of grade 3 or greater toxicity (stomatitis, diarrhea or fatigue). While this combination has some activity against pancreatic cancer, its toxicity limits its potential as a palliative treatment.

Fish consumption and breast cancer risk: an ecological study.

There is experimental evidence that fish oils protect against mammary carcinogens in animals. However, there has been little investigation of the possible relevance of this finding to breast cancer in humans. We compared breast cancer incidence and mortality rates with estimates of the consumption of fish and other foods and nutrients in the countries for which reliable data are available. The results showed an inverse association between percent calories from fish and breast cancer rates that was consistent with a protective effect. This analysis confirmed the finding of others that dietary fat is strongly associated with international variation in breast cancer rates. It also showed that of the dietary components considered, percent calories from fish was the factor most strongly correlated with breast cancer rates after statistical adjustment for dietary fat intake. This result is therefore in accord with animal experimental data and suggests that the omega-3 fatty acids contained in certain fish may protect against breast cancer.

Psychometric properties and responsiveness of the EORTC quality of Life Questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer.

The QLQ-C30, a health-related quality of life questionnaire developed for use in patients with cancer, has been previously validated in patients with lung cancer and head and neck cancer. In this study, further validation was carried out for 535 patients, including patients with breast cancer (n = 143) and ovarian cancer (n = 111) for whom there is no previously published validation, as well as patients with lung cancer (n = 160) and a heterogeneous group of other cancers (n = 121). All patients were entered in one of two trials of anti-emetics to prevent chemotherapy-induced emesis. The QLQ-C30 was completed before chemotherapy and on day 8 after chemotherapy. The factor structure in patients with breast and ovarian cancer was similar to that previously described. Interdomain correlations, in the entire group, were strongest for the physical and role function domains and the fatigue, pain and global quality of life domains before and after chemotherapy. In addition, after chemotherapy, social function was also strongly correlated with fatigue and global quality of life. These correlations were not always of equal strength in the breast, ovarian and lung groups, suggesting that there may be differences between these groups. The responsiveness of the QLQ-C30 in the presence of widely metastatic, as compared with locoregional, disease showed changes in the expected directions (i.e., diminished function in physical and social role functions and in global quality of life, with greater fatigue and pain in patients with metastatic disease). Eight days after chemotherapy, decreases were seen in physical, role and social functioning and in global quality of life, and there was greater fatigue, nausea and vomiting compared with before chemotherapy. Patients with breast cancer had better physical, role and social functioning and less fatigue and pain than patients with ovarian cancer. This result is expected, since many of the patients with breast cancer had early stage disease, whereas those with ovarian cancer had advanced stage disease. Mean scores for patients with lung cancer were between the other two groups, in keeping with the mixture of early and advanced stage disease in these patients. There was a strong correlation between ECOG performance status scores and several domains of the QLQ-C30; these were all in the expected directions. The results of this study confirm those in earlier studies on patients with lung cancer, and provide new information on patients with breast and ovarian cancer. In addition, the QLQ-C30 is responsive to the effects of chemotherapy and of metastatic disease.