Lymphomas in pregnancy.

Lymphoma in pregnancy is an uncommon occurrence. This diagnosis is challenging, and a multidisciplinary team of specialists in obstetrics, anesthesiology, neonatology, hematology psychology should participate in the management of this condition. The choice of treatment regimen depends on the histotype and the gestational age. In Hodgkin lymphoma, ABVD is safe if administered after the thirteenth week of pregnancy. In indolent non-Hodgkin Lymphomas (NHL) a watchful waiting approach is reasonable; in case of aggressive NHLs, if the diagnosis occurs in the first gestational weeks, a termination of the pregnancy might be considered or if it occurs after the thirteenth week of pregnancy, a standard R-CHOP regimen is safe. Regarding new anti-lymphoma drugs, available data on the potential fetotoxicity of these agents are limited. Data collection regarding the use of new drugs in pregnant patients is mandatory in order to learn more about their safety and facilitating clinical decision making in this setting of patients.

Characterization of the immune environment in pregnancy-associated breast cancer.

Pregnancy-associated breast cancer (PrBC) is a rare and clinically challenging condition. Specific immune mechanisms and pathways are involved in maternal-fetal tolerance and tumor-host immunoediting. The comprehension of the molecular processes underpinning this immune synergy in PrBC is needed to improve patients' clinical management. Only a few studies focused on the immune biology of PrBC and attempted to identify bona fide biomarkers. Therefore, clinically actionable information remains extremely puzzling for these patients. In this review article, we discuss the current knowledge on the immune environment of PrBC, in comparison with pregnancy-unrelated breast cancer and in the context of maternal immune changes during pregnancy. A particular emphasis is given to the actual role of potential immune-related biomarkers for PrBC clinical management.

Pregnancy-associated breast cancer (PrBC) affects about 4% of women with breast cancer who are of childbearing age. Managing these tumors is difficult due to interactions between the mother, fetus and tumor. These interactions cause changes in the immune system of patients with PrBC. Understanding how the immune system responds to PrBC may lead to better ways of managing the disease. This review focuses on the current knowledge of the immune system in PrBC, including which components can be used as biomarkers to improve clinical management.

Cancer Predisposition Genes in Adolescents and Young Adults (AYAs): a Review Paper from the Italian AYA Working Group.

PURPOSE OF REVIEW: The present narrative systematic review summarizes current knowledge on germline gene mutations predisposing to solid tumors in adolescents and young adults (AYAs). RECENT FINDINGS: AYAs with cancer represent a particular group of patients with specific challenging characteristics and yet unmet needs. A significant percentage of AYA patients carry pathogenic or likely pathogenic variants (PV/LPVs) in cancer predisposition genes. Nevertheless, knowledge on spectrum, frequency, and clinical implications of germline variants in AYAs with solid tumors is limited. The identification of PV/LPV in AYA is especially critical given the need for appropriate communicative strategies, risk of second primary cancers, need for personalized long-term surveillance, potential reproductive implications, and cascade testing of at-risk family members. Moreover, these gene alterations may potentially provide novel biomarkers and therapeutic targets that are lacking in AYA patients. Among young adults with early-onset phenotypes of malignancies typically presenting at later ages, the increased prevalence of germline PV/LPVs supports a role for genetic counseling and testing irrespective of tumor type.

Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting.

BACKGROUND: Healthy individuals and patients with cancer who are carriers of germline pathogenic variants in the BRCA1/2 genes face multiple reproductive challenges that require appropriate counseling and specific expertise. MAIN BODY: On December 5th-7th, 2019, patient advocates and physicians with expertise in the field of reproductive medicine, fertility preservation, and oncology were invited to "San Giuseppe Moscati" Hospital in Avellino (Italy) for a workshop on reproductive management of women with germline pathogenic variants in the BRCA1/2 genes. From the discussion regarding the current evidence and future prospective in the field, eight main research questions were formulated and eight recommendations were developed regarding fertility, fertility preservation, preimplantation genetic testing, and pregnancy in healthy carriers and patients with cancer. CONCLUSION: Several misconceptions about the topic persist among health care providers and patients often resulting in a discontinuous and suboptimal management. With the aim to offer patient-tailored counseling about reproductive issues, both awareness of current evidences and research should be promoted.

Exploring differences in psychological aspects during pregnancy between cancer survivors and women without a history of cancer.

Young cancer survivors often wish to bear a child after oncological treatments, as they might not have started or completed their families. As young cancer survivors have a higher risk of developing psychological difficulties, this study investigated whether there were significant differences in psychological aspects between pregnant women who received a cancer diagnosis in the past and pregnant women without a history of cancer. A total of 123 pregnant women, of which 36 were cancer survivors and 87 women without a history of cancer, were recruited during their last trimester at different hospitals in Northern Italy. Patients were asked to complete a socio-demographic profile and questionnaires measuring mood states, post-traumatic symptoms, centrality of the pregnancy and cancer event, quality of life, and prenatal attachment. Cancer survivors had significantly higher levels of PTSD symptoms, perceived pregnancy as more central to their identity and life story, perceived lower quality of life and had lower intensity of prenatal attachment compared with the control group. Centrality of the cancer event did not correlate with any psychological variables. Preliminary results suggest that a past cancer diagnosis can influence the mother's psychological functioning and the development of the relationship with their child.

Seeing beyond COVID-19: understanding the impact of the pandemic on oncology, and the importance of preparedness.

The impact of this pandemic is not only through COVID-19 itself: the care for non-COVID-19 related conditions has been dramatically curtailed, shaking entire healthcare services around the world. Amongst the non-COVID-19 related conditions, oncology has been disproportionally affected. We discuss how oncology has changed since the acute phase of the pandemic; its impact on clinicians, trainees, and patients; and offer some medical and historical perspectives to reflect on how this impact could be reduced.

Fertility preservation in women harboring deleterious BRCA mutations: ready for prime time?

Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted.

Frequency of Pregnancy Related Cancer: A Population Based Linkage Study in Lombardy, Italy.

OBJECTIVES: The aims of this study were to estimate the occurrence of pregnancy-associated cancer overall and by site, to evaluate if the risk increases over time, and to investigate some major determinants. METHODS: This is a population-based linkage study using the regional hospital discharge forms [Scheda di Dimissione Ospedaliera (SDO)] database of Lombardy, Italy, a region with 10 million inhabitants. All resident women with a SDO reporting a birth or abortion between 2001 and 2012 were identified. Pregnancy-associated cancers were defined as a cancer occurring during pregnancy or within 12 months after pregnancy and were identified by selecting all SDOs reporting a first diagnosis of cancer. Risk of developing a pregnancy-related cancer was calculated as the ratio of the number of pregnancy-related cancers to the total number of pregnancies. The effect of potential predictors on the risk was estimated using a logistic regression model, and odds ratios (OR) were estimated. RESULTS: During the period 2001-2012, the risk of pregnancy-related cancer was 122.9 per 100,000 pregnancies. The most common cancers were breast cancer (479 cases, 39.9/100,000 pregnancies), thyroid cancer (186 cases, 15.5/100,000), and lymphomas (157 cases, 13.1/100,000). Skin cancer accounted for 177 cases (14.8/100,000), half of which were melanomas. The risk of developing a pregnancy-related cancer increased significantly with age, from 60 of 100,000 for women less than 30 years old to 265 of 100,000 for women aged more than 40 years. Italian women had a higher risk than foreign ones (OR, 1.6), and the pregnancy outcome was more frequently an abortion (OR, 1.2), whereas no trend in risk was observed with calendar year (P = 0.249). CONCLUSIONS: This study confirms previously reported incidence estimates but does not show increases over time.

Fertility-Sparing Options in Young Women with Cervical Cancer.

OPINION STATEMENT: Cervical cancer (CC) is the fourth most frequent tumor and the fourth most common cause of cancer death among women worldwide. Furthermore, more than 40 % of women with early CC are affected during reproductive age and wish to remain fertile. Thus, many patients demand a more conservative policy for managing these lesions in order to have an uneventful pregnancy in the near future. For this reason, interest in fertility preservation strategies has been increasing, and the number of published studies on this topic has grown significantly. Conization was the first fertility-sparing surgical procedure tested in stage IA1 CC. However, in recent decades, other strategies have been tested, particularly for more advanced tumors. The aim of this review is to analyze the main techniques performed in patients with CC who are eligible for fertility-sparing surgery, with particular attention paid to open questions and controversies.

Difficult choices for young patients with cancer: the supportive role of decisional counseling.

PURPOSE: The aim of patient decisional support interventions is to promote shared decision making. Many of these interventions are comprehensive of information and guidance. In this pilot study, we evaluate the effects of a decision-making support (decision counseling (DeCo)) on decision making, decisional conflict, and anxiety in cancer patients facing with values-based decisions on fertility and procreation or genetic testing and risk reduction options in oncology. METHODS: DeCo was proposed during the medical consultation. The following questionnaires were administered to 54 patients before the DeCo session and 1 week after it: stage of decision making (SDM), decisional conflict scale (DCS) and subscales ("uncertainty," "informed," "clarity," "support," and "effective decision"), state-trait anxiety inventory. Decision Support Questionnaire and Usefulness of Decision Counseling were created ad hoc for this study. Multivariate logistic models and ANCOVA models were used to investigate the changes of SDM and DCS in association with DeCo. RESULTS: We found a significant improving in SDM with DeCo (P = 0.01) and a significant reduction in DCS with DeCo (P = 0.007) measured with the Decision Support Questionnaire. In particular, the DCS informed subscale showed a significant decrease in time (P = 0.002). CONCLUSION: DeCo is useful to facilitate decision making and reduce decisional conflict. It plays a role in the perception of being informed while not directly providing clinical information. This model of decisional support intervention, in which information is provided only by the clinician and decisional support is focused on personal aspects that influence the decision, could improve shared decision making between patient and clinicians.

Attitudes on fertility issues in breast cancer patients: an Italian survey.

BACKGROUND: Fertility issues should be discussed with young women before the start of any anticancer treatment. The study is aimed to investigate the attitude on fertility among Italian oncologists and breast surgeons dealing with BCa, and to report the consensus achieved on specific statements. METHODS: One hundred and sixty-two panelists anonymously expressed an opinion through a web-based platform on 19 statements based on the Delphi method. RESULTS: Ninety-one percent of oncologists considered important to discuss with patients about fertility issues and 83% believed estrogens could stimulate the growth of hidden cancer cells in ER(+) tumors. Difficulties in accessing fertility preservation procedures were mainly due to patients' reluctance, but also to lack of coordination with the assisted reproduction specialists. No full consensus was reached on the prognostic role of pregnancy after BCa. Fifty-four percent of oncologists declared that pregnancy does not affect oncologic prognosis. Treatment with GnRHa during chemotherapy was considered the only mean for preserving ovarian function. CONCLUSIONS: Fertility preservation in BCa patients is a well-accepted practice among Italian oncologists. A poor knowledge of this specific issue emerged from the survey, even if a certain degree of agreement was observed on most fertility-related issues.

Treatment options for pregnant women with ovarian tumors.

Diagnosis of ovarian mass during pregnancy is a rare event. Treatment of ovarian malignancies during pregnancy depends on histology, grade, stage, and gestational weeks. When possible, surgical excision is indicated, and sometimes, fertility-sparing surgery is recommended. Administration of systemic treatment before or after surgery is indicated as in nonpregnant women. Preliminary data suggest that platinum salts and taxanes are safe during pregnancy. Management of ovarian tumors in pregnancy requires a multidisciplinary approach to guarantee an optimal treatment for the mother and the fetus.

Caring for Pregnant Patients with Cancer: A Framework for Ethical and Patient-Centred Care.

(1) Background: Caring for pregnant cancer patients is clinically and ethically complex. There is no structured ethical guidance for healthcare professionals caring for these patients. (2) Objective: This concept paper proposes a theoretically grounded framework to support ethical and patient-centred care of pregnant cancer patients. (3) Methodological approach: The framework development was based on ethical models applicable to cancer care during pregnancy-namely principle-based approaches (biomedical ethics principles developed by Beauchamp and Childress and the European principles in bioethics and biolaw) and relational, patient-focused approaches (relational ethics, ethics of care and medical maternalism)-and informed by a systematic review of clinical practice guidelines. (4) Results: Five foundational discussion themes, summarising the key ethical considerations that should be taken into account by healthcare professionals while discussing treatment and care options with these patients, were identified. This was further developed into a comprehensive ethics checklist that can be used during clinical appointments and highlights the need for a holistic view to patient treatment, care and counselling while providing ethical, patient-centric care. (5) Conclusion: The proposed framework was further operationalised into an ethics checklist for healthcare professionals that aims to help them anticipate and address ethical concerns that may arise when attending to pregnant cancer patients. Further studies exploring clinicians' attitudes towards cancer treatment in the course of pregnancy and patient experiences when diagnosed with cancer while pregnant and wider stakeholder engagement are needed to inform the development of further ethical, patient-centred guidance.

The Oncohumanities training programme: Fostering a deeper engagement and integration of oncology and humanities to tackle the pressing and complex challenges of cancer care.

'Oncohumanities' is a new field of oncology and humanities which integrates a rich gamut of humanity disciplines and oncological expertise to tackle patients' real needs and priorities. To promote knowledge and awareness on this topic, we propose a training programme that will blend conceptual knowledge underpinning oncology practice with and person-centred care based on the humanisations of care, on empowerment of patients, and on respect for their diversities. Oncohumanities differs from most existing medical humanities training as it is integrated and engaged with oncology (rather than an add-on). This means that its agenda is driven by the real needs and priorities arising out of daily oncological practice. It is our hope that this new Oncohumanities programme and approach will contribute to guiding future efforts to foster a strong integrated partnership between humanities and oncology.

Psychological issues in breast cancer survivors confronted with motherhood: Literature review and a call to action.

Breast cancer is currently the most common cancer among women worldwide; in 15-25% of cases, patients are premenopausal at the time of diagnosis, and 50% of women desire pregnancy after cancer diagnosis. Motherhood after breast cancer involves complex psychological challenges with long-term consequences, though it is safely pursuable with adequate support. The purpose of this mini-review is to analyze the psychological implications surrounding pregnancy and motherhood after breast cancer and promote action in addressing the challenges that might affect women facing these life events.

Review Article a Multidisciplinary Evaluation for Advanced Supportive Care of Breast Cancer Patients.

Background: Cancer cases diagnosed each year are increasing, mainly because the population is ageing and, in part, due to early detection. This implies that there are more and more persons that receive medical anticancer therapies and that are interested in maintaining their quality of life. Many oncological treatments, including chemotherapy, immunotherapy, surgery, and radiotherapy, and combined therapy are associated with cutaneous toxicity and long-term side effects to different tissues and organs. This is particularly relevant when new therapies are used since these may cause new and unexpected side effects that may be short-lived but, in some cases, may become chronic or permanent. Patients often seek advice with their oncologists on what can be done and what cannot be done. Notably, many of the cutaneous side effects can be prevented or reduced by adequate interventions. Summary: The aim of this review is to highlight how oncological patients may benefit from a closer collaboration between specialists in different branches. We will focus on women with breast cancer since we think that they may derive a special benefit from this collaboration, but we will analyse other cancers in future papers. Key Messages: The working group was created to help the medical doctor in the prevention and management of all the adverse effects of the oncological treatments, supporting patients in this phase of their life, including nutritional assessment and dietary support.

Fertility preservation and monitoring in adult patients diagnosed with lymphoma: consensus-based practical recommendations by the Fondazione Italiana Linfomi & Società Italiana della Riproduzione Umana.

Introduction: Fertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship. Methods: For the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel's activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin's lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology. Results: From the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations. Discussion: These recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway.

Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features.

PURPOSE: Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, regardless of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth in the mammary gland. However, in women, the molecular mechanisms that underlie this poor prognosis of patients with PP-BCPW remain vastly underexplored, due to of lack of adequate patient numbers and outcome data. EXPERIMENTAL DESIGN: We explored whether distinct prognostic features, common to all breast cancer molecular subtypes, exist in postpartum tumor tissue. Using detailed breastfeeding data, we delineated the postweaning period in PP-BC as a surrogate for mammary gland involution and performed whole transcriptome sequencing, immunohistochemical, and (multiplex) immunofluorescent analyses on tumor tissue of patients with PP-BCPW, PP-BCDL, Pr-BC, and NP-BC. RESULTS: We found that patients with PP-BCPW having a low expression level of an immunoglobulin gene signature, but high infiltration of plasma B cells, have an increased risk for metastasis and death. Although PP-BCPW tumor tissue was also characterized by an increase in CD8+ cytotoxic T cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups. CONCLUSIONS: These data point to the importance of plasma B cells in the postweaning mammary tumor microenvironment regarding the poor prognosis of PP-BCPW patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young patients with breast cancer.