Oncological Treatment Research Articles

Pre- and Post-Operative Quality of Life in Patients with Osteoradionecrosis of the Jaw.

Osteoradionecrosis of the jaw (ORNJ) is a feared complication following radiation therapy performed for oncological treatment of head and neck cancers (HNC). To date, there is no clear evidence regarding the impact of surgical treatment of ORNJ on the quality of life (QoL) of affected patients. However, understanding the significance of the surgical treatment approach and its effects on QoL is an essential factor in the decision-making process for optimal, individualized therapy. In this prospective clinical study, QoL was assessed in relation to health related QoL (HRQoL) and oral health related QoL (OHQoL) before and after surgical treatment of ORNJ using standardized questionnaires (EORTC QLQ-C30, QLQ-HN35, OHIP-14). The overall QoL scores as well as individual domains of the collected scales regarding functional and symptom-related complaints were statistically analyzed. Subgroups concerning age, gender, different risk factors and type of ORNJ therapy were compared using Kruskal Wallis test. In addition, clinical and demographic patient data were collected and analyzed. QoL improvement correlated with the type of surgical ORNJ and the length of hospitalization. Better QoL scores were achieved post-operatively regarding different symptoms like pain, swallowing and mouth opening. Long-term effects of radiation therapy remained visibly restrictive to QoL and worsen over time.

NFS-01. EXTREMELY RARE CASE OF CHILDREN WITH NIJMEGEN BREAKAGE SYNDROME AND MEDULLOBLASTOMA – A THERAPEUTIC CHALLENGE

Abstract BACKGROUND Nijmegen Breakage Syndrome (NBS) is an autosomal recessive inherited disorder characterized by DNA repair abnormalities. It manifests with heightened sensitivity to radiotherapy (RT) and predisposes individuals to neoplastic diseases. Antineoplastic treatment in NBS patients is particularly challenging due to concurrent immune disorders, intense toxicities, and contraindications for RT. Hematologic disorders, especially lymphomas, are among the most prevalent malignancies in NBS patients. Solid tumors in NBS are extremely rare, with only two pediatric cases documented in the literature, both succumbing due to severe complications of treatment. METHODS A review and analysis of the medical documentation of a child with NBS and MB treated at the Department of Pediatrics, Hematology, and Oncology, Gdansk, Poland, were conducted. RESULTS A genetically confirmed NBS girl displaying typical phenotypic features presents symptoms at the age of 2 years, such as headaches, reluctance to walk, and drowsiness. Imaging confirmed a tumor in the left cerebellar hemisphere, measuring 40x33x30mm, displaying radiological features consistent with Medulloblastoma (MB). The patient underwent gross total resection of the tumor. The pathology revealed a desmoplastic type of MB with SHH activation, TP53 wild type, and ongoing molecular analysis. Postoperative imaging confirmed clinical remission, and cerebrospinal fluid examination was negative. Considering the substantial toxicities of chemotherapy in NBS patients and the contraindications for RT, the patient received chemotherapy with reduced cytostatic doses. Treatment was complicated by profound and prolonged myelosuppression and infections. Currently, after completing six cycles of chemotherapy, the patient is still in remission. To maintain remission and address NBS, the patient will receive allogeneic bone marrow transplantation from a 9/10 HLA-matched unrelated donor. CONCLUSIONS Managing patients with NBS, complicated by neoplastic diseases, is exceptionally demanding and necessitates an individualized multidisciplinary approach. Modern diagnostic and therapeutic methods enhance the prospects of reducing the toxicity of oncologic treatment, improving quality of life, and extending overall survival.

NFS-05. INCIDENCE OF BEVACIZUMAB ASSOCIATED TOXICITY IN CHILDREN WITH LOW GRADE GLIOMA WITH AND WITHOUT NF1

Abstract BACKGROUND Low grade gliomas (LGG), both sporadic & Neurofibromatosis1 (NF1) associated, are the commonest pediatric brain tumors. When surgically unresectable, they may become progressive/ symptomatic and require chronic oncological treatment. Bevacizumab (BVZ; Avastin), a recombinant humanized monoclonal antibody to VEGF, has shown efficacy both as a single agent or combined with chemotherapy as second/ third line treatment of progressive LGG especially in the optic pathway. BVZ can be associated with adverse effects including hypertension (HTN) and proteinuria. Children with NF1 have known increased tendency to hypertension however there is no data comparing the frequency of side effects from BVZ in patients with or without NF1. METHODS Retrospective study of all LGG cases treated with BVZ diagnosed 2010-2023 in a tertiary oncology center. We graded hypertension, proteinuria, cardiac function, retinopathy & bleeding according to the CTCAE v5.0 in NF1 and non-NF1 patients. RESULTS 16 children with LGG were treated with BVZ; 7 had NF1. 75% optic glioma, 25% other. All received BVZ as second or third line treatment in combination with chemotherapy. In the non NF1 group, 77% patients developed grade 2 HTN on BVZ treatment; none required medical intervention. 6 had grade 1 elevation of protein-creatinine ratio (median 0.38). In the NF1 group, 71% developed grade 2 or 3 HTN on BVZ treatment including a patient with aortic coarctation (CoA) who had worsening of previous HTN, 2 required antihypertensive therapy (p non-significant HTN non NF1 vs. NF1). Only 1 NF1 patient developed proteinuria. No patients in either group stopped BVZ prematurely for toxicity. Hypertension was reversible after cessation of BVZ in all except the patient with CoA. CONCLUSIONS Hypertension is more common than previously reported in both NF1 and non-NF1 patients treated with BVZ for LGG. Blood pressure should be monitored and treated appropriately. BVZ is safe in young patients with NF1.

A Preliminary Study Examining the Correlation between EGFRI Treatment, Clinic Dermatoscopy Features, and Serum Levels of Anti-Alpha-Galactosyl IgE in Colorectal Cancer Patients

The introduction of molecularly targeted therapies, particularly the epidermal growth factor receptor inhibitors (EGFRIs), has had a positive impact by increasing the life expectancy of patients with advanced colorectal cancer (CRC). The most used anti-EGFRIs monoclonal antagonist, Cetuximab, induces skin responses in most patients, leading to a reduction of dosages or even therapy discontinuation, all with devastating effects. Our study aimed to assess the predictive role and the possible correlations of clinical features, imaging aspects (dermatoscopy), and laboratory tests (anti-alpha-galactosyl IgE levels) for early detection of Cetuximab skin toxicity in patients with metastatic CRC. The association of IgE antibodies against goat alpha-1,3-galactose serum levels with various degrees of skin toxicity encountered during the oncologic treatment resulted in higher concentrations in patients with pruritus and hair changes. Incorporating dermatoscopy into the routine dermatological consultation allowed us to perform a severity assessment, dynamically record, and identify even the erupting lesions previously invisible to classical examination. Hence, we were enabled to generate a broad report and to classify various degrees of skin toxicity severity linked to Cetuximab treatment in 19 patients with metastatic CRC. Detecting the emergent lesions and initiating dermatological treatment in the early stages decreased the severity of skin toxicity. As a result, the duration of the antibiotic treatment was much shorter, and the risk of dose reduction or interruption of the cancer treatment was diminished. In conclusion, we emphasize the need for a regular dermatological examination with dermatoscopy of CRC patients undergoing Cetuximab treatment. Skin toxicity is a significant concern for these patients, and healthcare providers should be vigilant in monitoring and managing this side effect in order to optimize patient care. The correlation between anti-alpha-Gal IgE levels and Cetuximab-induced skin toxicities is an emerging area. More extensive studies need to be published in order to establish this relationship directly.

Prospective study on health-related quality of life, oral mucositis and oral health on during treatment of head and neck cancer

BackgroundFew studies have examined health related Quality of Life (HR-QoL) during the treatment of head and neck cancer (HNC) with even fewer focusing on the impact of oral mucositis (OM) on HR-QoL. Studies performed during treatment of HNC makes it possible to follow fluctuations in HR-QoL, OM and other treatment related side effects. The aim was to prospectively analyze HR-QoL, changes in clinical variables and the impact of OM on HR-QoL during HNC treatment.Materials and methodsPatients were recruited before commencing curative cancer treatment and were given professional oral care weekly during oncologic treatment. HR-QoL was reported before, during (week 2, 4 and 6) and three months after treatment using the EORTC Quality of Life questionnaires C30 and H&N35 and the stimulated whole salivary secretion rate was determined at the same time-points. OM (erythema and ulceration) was registered using the Oral Mucositis Assessment Scale (OMAS), at baseline, weekly during treatment and post treatment. Differences in HR-QoL between different timepoints were analyzed. To analyze the impact of OM on HR-QoL the patients were categorized into two groups: no/mild OM (OMAS ulceration score 0–1) or severe OM (OMAS ulceration score ≥ 2) and HR-QoL was compared between the two OM groups at three timepoints during treatment.ResultsFifty-seven patients (43 men, 14 women), with a mean age of 58 years were included. Patients reported progressively impaired HR-QoL, with peak issues noted at weeks 4 and 6, particularly in social eating, senses, appetite loss, sticky saliva, and decreasing salivary secretion rates were determined. Patients with severe OM reported worse HR-QoL compared to those with no/mild OM. Persistent problems 3 months post treatment were appetite loss, dry mouth, senses (smell and taste) and problems with social eating.ConclusionPatients experienced exacerbated symptoms and problems weeks 4 and 6 of oncological treatment, especially among those with severe OM, stressing the importance of clinically monitoring the patients to reduce and alleviate their symptoms. Persistent problems three months post treatment are likely associated with the reduced salivary secretion rate indicating that patients should be monitored also after completed oncological treatment.

EE435 Hospitalization Costs of Common Grade 3/4 Adverse Events Associated With Oncology Treatments in the United States

EE435 Hospitalization Costs of Common Grade 3/4 Adverse Events Associated With Oncology Treatments in the United States

The Combination of Gefitinib and Acetaminophen Exacerbates Hepatotoxicity via ROS-Mediated Apoptosis.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it need for analgesics during oncology treatment, particularly in the context ofthe coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Resection of intrahepatic cholangiocarcinoma in octogenarians: a single-center analysis

The rapidly aging population in industrialized countries comes with an increased incidence of intrahepatic cholangiocarcinoma (iCC) which presents new challenges for oncological treatments especially in elderly patients. Thus, the question arises to what extent the benefit of surgical resections, as the only curative treatment option, outweighs possible perioperative risks in patients ≥ 80 years of age (octogenarians). We therefore retrospectively analyzed 311 patients who underwent resection for iCC at Hannover Medical School between January 1996 and December 2022. In total, there were 11 patients older than 80 years in our collective. Despite similar tumor size, octogenarians underwent comparatively less extensive surgery (54.5% major resections in octogenarians vs. 82.7% in all other patients; p = 0.033) with comparable rates of lymphadenectomy and tumor-free resection margins. Furthermore, we did not observe increased major postoperative morbidity (Clavien-Dindo ≥ IIIa complications: 27.3% vs. 34.3% in all other patients; p = 0.754) or mortality (estimated 1-year OS of 70.7% vs. 72.5% in all other patients, p = 0.099). The length of intensive care unit (ICU) or intermediate care unit (IMC) stay was significantly longer in octogenarians, however, with a comparable length in total hospital stay. The estimated overall survival (OS) did also not differ significantly, although a trend towards reduced long-term survival was observed (14.5 months vs. 28.03 months in all other patients; p = 0.099). In conclusion, primary resection is a justifiable and safe therapeutic option even in octogenarians but requires an even more thorough preoperative patient selection.

Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center

Insurance barriers to cancer care can cause significant patient and clinician burden. To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Insurance denial for RT. Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Pharmaceutical company funding of cancer patient advocacy organizations in the Netherlands

BackgroundFinancial conflicts of interest (FCOI) of medical professionals and associated organizations with pharmaceutical companies (pharma) might contribute to the use of low value oncological treatments. Value criteria for oncological drug approvals in the Netherlands have recently become more stringent leading to objections by cancer patient advocacy organizations (cPAOs). Considering the importance of cPAOs input in cancer patient care we analyzed whether pharma funding of cPAOs occurs in the Netherlands. MethodsThe cPAO websites and available annual reports were evaluated for disclosure of pharma funding for the years 2021 and 2022. Also, data from the Dutch Healthcare Transparency Registry (DHTR) were extracted. ResultsTwenty-one of 34 (61.8 %) cPAOs received pharma funding (with 20 registered in the DHTR), and for 13 (29.4 %) cPAOs no reporting of pharma funding could be found. Three of the cPAOs disclosed pharma funding directly on their main website. Online educational material was available from 22 cPAOs on their websites with pharma funding disclosed on the educational material in 5. The total registered amount of pharmaceutical funding was €667,232.00 in 2021 and €536,098.00 in 2022. The median (and interquartile ranges) DHTR registered amount of support per cPAO that received funding in the studied period was €23,799.50 (14,823.75–84,663.30). The most common funding category as defined in the DHTR was project sponsorship. ConclusionsFinancial support by the pharmaceutical industry is common for Dutch cPAOs. Given the importance of cPAOs and their objective input in the societal debate on the availability of cancer drugs, the potential influence of pharma sponsoring should be critically evaluated.

Pain, symptoms and therapy satisfaction in adult oncologic patients at admission to palliative care: An Italian prospective, multicenter, observational study.

Pain in cancer patients is a complex clinical problem. Pain is systematically assessed and treated during palliative care, but little is known about how it is addressed before starting palliative care. This study primarily analyzed pain, symptoms, ongoing therapy at patients' admittance to the palliative care unit, and the relationships between pain and tumor, comorbidities, performance status and quality of life (QoL). Notably, patient satisfaction with the received antalgic therapy was assessed. A multicentric, prospective, observational study was conducted in seven Italian palliative centers. The population consisted of adult cancer patients admitted to specialist palliative care units in hospice and home care. The sample consisted of 476 patients. Ninety-three patients reported moderate pain of 4.0 and worst pain of 5.9 at the initial medical examination. The pain was high, and QoL was lower in breakthrough pain. The pain was lower in older subjects when it was discontinuous and when it was also treated with corticosteroids. A total of 61% of the patients were unsatisfied with the prescribed pain therapy. Before the beginning of palliative care, physicians do not manage pain adequately. We support the idea that palliative care is not only intended for the last days of life but must be started early and simultaneously with oncological treatments. All that, in our opinion, is often ignored, and we hope that our study could have a positive influence and that the study results stimulate further research in this area with in-depth studies.

Participants’ perceptions support the coexistence of benefits and burdens of cancer clinical trial participation

Background To advance oncology treatment for adults, comprehensive understanding of how and why people decide to enroll in, remain in, and withdraw from cancer clinical trials is needed. While quantitative findings provide insights into these benefits and burdens, they provide limited understanding of how adults with cancer appraise their situation and approach decisions to undertake a clinical trial. The goal of this mixed methods analysis was to conceptualize participants’ assessment of benefits and burdens related to cancer clinical trial participation. Materials and methods This sub-group analysis of 21 participants was part of a larger sequential, explanatory mixed methods study. We used Creamer’s integrated approach to linking quantitative and qualitative data to assess convergence, with qualitative data explaining quantitative results. Participants were grouped into four categories based on quantitative benefit/burden scores and thematic analysis of their qualitative data was used to describe these categories. Results Across groups participants varied in descriptions of benefits and burdens of cancer clinical trial participation and reasons for participating. Those reporting high benefit/low burden described “seizing the opportunity to participate;” those reporting low benefit/low burden described “taking responsibility” through trial participation; those reporting low benefit/high burden described how they were “willing to endure,” and those with high benefit/high burden emphasized “deciding to act.” Conclusions Participants’ qualitative descriptions of benefits and burdens were more nuanced and dynamic than reflected in their quantitative ratings. Thus, current measures may be missing important concepts, such as logistic challenges of trial participation. Our results have implications for consenting procedures and decisional support guidance offered to patients and their caregivers.

Risk Factors for Recurrence After Surgery for Rectal Cancer in a Modern, Nationwide Population-Based Cohort

BackgroundThe success of modern multimodal treatment in rectal cancer is dependent on risk prediction. Better knowledge of the risk of locoregional and distant recurrence, in relation to preoperative treatment, pathological stage, and commonly used risk factors, is needed when deciding on adjuvant therapy and surveillance.MethodsThe Swedish ColoRectal Cancer Registry was used to identify patients diagnosed with rectal adenocarcinoma between 2011 and 2018. Readily available variables, including patient, tumor, and treatment factors were exposures. Cox proportional hazard models were used to identify important risk factors for recurrence and calculate recurrence risks.ResultsA total of 9428 curatively resected patients were included and followed for a median of 72 months. Eighteen percent had distal recurrence and 3% had locoregional recurrence at 5 years. Risk factors with major impact on distal recurrence were pT4a (hazard ratio [HR] 5.1, 95% confidence interval [CI] 3.3–8.0), pN2b (HR 3.4, 95% CI 2.7–4.2), tumor deposit (HR 1.7, 95% CI 1.5–1.9), lymph node yield (HR 1.5, 95% CI 1.3–1.8), and tumor level 0–5 cm (HR 1.5, 95% CI 1.3–1.8). Pathologic stage and number of risk factors identified groups with markedly different recurrence risks in all neoadjuvant treatment groups.ConclusionsReadily available risk factors, as a complement to stage, are still valid and robust in all neoadjuvant treatment groups. Tumor deposit is important, while circumferential resection margin might no longer be important with improved oncological treatments and high-quality TME surgery. Tailored surveillance is possible in selected groups using risk stratification based on stage and risk factors.

Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study

BackgroundCancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. MethodsWe conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). ResultsThe humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. ConclusionsCancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.

Utilidad en la prevención, tratamiento y pronóstico de la medicina de precisión en oncología

Introduction: advances in genetics in recent decades has ushered a new era. Precision medicine has used these advances to play an increasingly important role in cancer prevention, diagnosis and treatment. Objetive: was to evaluate the usefulness of precisión medicine in improving prevention, treatment and prognosis in oncology. Discussion: studies on carcinogenesis have propelled the discovery of crucial events in the development of malignant neoplasms, identifying specific molecular subtypes of several common tumors. This has resulted in a better charaterization of tumors, which previously depended only on anatomapathological findings, and has enabled the development of new drugs, which have shifted the oncologic care paradigm. The identification of mutations that may determine predisposition to cancer, such as, BRCA mutations in breast cáncer, has facilitated screening to identify patients and help improve decision making and modify risk. Conclusions: the efficacy of various antitumor therapies suggests the beginning of an era in which preventive actions and clinical decisions will be based on the profile of genetic abnormalities of the tumor, improving patient prognosis and quality of life. This will allow an increase in the use of this type of precision treatments based on the profile of genetic changes.

CAR-T cell therapy in advanced thyroid cancer: from basic to clinical.

The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field.

Fertility Preservation and Ovarian Hyperstimulation Syndrome Management in Cancer Care: A Pathophysiological Perspective on Gonadotropin-Releasing Hormone Agonists and Antagonists.

This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted, and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the 'flare-up' effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and the management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.

Integrating system biology and intratumor gene therapy by trans-complementing the appropriate co-stimulatory molecule as payload in oncolytic herpes virus

Systems biology has been applied at the multi-scale level within the cancer field, improving cancer prevention, diagnosis and enabling precision medicine approaches. While systems biology can expand the knowledge and skills for oncological treatment, it also represents a challenging expedition due to cancer complexity, heterogeneity and diversity not only between different cancer indications, but also in its evolution process through space and time. Here, by characterizing the transcriptional perturbations of the tumor microenvironment induced by oncolytic, we aimed to rationally design a novel armed oncolytic herpes virus. We found that intratumor oncovirotherapy with HSV-1 induces T-cell activation signatures and transcriptionally activates several costimulatory molecules. We identified differentially expressed costimulatory receptors and binding partners, where inducible co-stimulators (ICOS) resulted in the potentially most beneficial targeted therapy. Through an ex-vivo transcriptomic analysis, we explored the potential of arming an oncolytic virus as a combination therapy strategy; in particular, we engineered a targeted herpes virus encoding ICOSL (THV_ICOSL), which resulted in a significant improvement in tumor size control compared to unarmed parental virus. Also, combination with a PD-1 inhibitor enhanced antitumor efficacy as predictable by upregulation of PD-1 and ligands pair (PD-L1/PD-L2) upon oncolytic virus injection. Generation of the human version of this virus encoding hICOSL orthologue effectively and specifically activated human T cells by triggering the ICOS pathway. Our data support the data-driven generation of armed oncolytic viruses as combination immunotherapeutic with checkpoint inhibitors.

"A very difficult conversation": Challenges and opportunities for improvement in pediatric oncology clinician communication about late effects.

Current approaches to communicating the potential late effects of pediatric oncology treatments leave many patients and families feeling unaware of risks and unprepared for the future. We aimed to identify provider perspectives on early communication about late effects. Semi-structured interviews were conducted with pediatric oncology providers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center from December 2021 to March 2022. Purposeful sampling ensured a diversity of clinical roles. Thematic analysis was conducted using deductive and inductive codes. We interviewed nine pediatric oncology providers; all expressed discomfort discussing potential late effects in early treatment conversations. Barriers to late effects communication included (i) social-emotional factors, including lack of perceived importance to families, worry about emotional burden on families, and provider feelings of helplessness/wanting to provide hope; and (ii) suboptimal set-up/resources, including limitations of consent forms, time constraints, and lack of available data. All providers supported the creation of a communication tool to assist early discussions of late effects. Communicating about late effect risks poses unique challenges to providers because of the perceived impact on families and the limitations of current practices and available resources. These findings support the need for a late effects communication tool to assist in early communication about late effects risks.

The impact of surgery and oncological treatment on risk of type 2 diabetes onset in patients with colorectal cancer: nationwide cohort study in Denmark

Background:Comorbidity with type 2 diabetes (T2D) results in worsening of cancer-specific and overall prognosis in colorectal cancer (CRC) patients. The treatment of CRC per se may be diabetogenic. We assessed the impact of different types of surgical cancer resections and oncological treatment on risk of T2D development in CRC patients.Methods:We developed a population-based cohort study including all Danish CRC patients, who had undergone CRC surgery between 2001 and 2018. Using nationwide register data, we identified and followed patients from date of surgery and until new onset of T2D, death, or end of follow-up.Results:In total, 46,373 CRC patients were included and divided into six groups according to type of surgical resection: 10,566 Right-No-Chemo (23%), 4645 Right-Chemo (10%), 10,151 Left-No-Chemo (22%), 5257 Left-Chemo (11%), 9618 Rectal-No-Chemo (21%), and 6136 Rectal-Chemo (13%). During 245,466 person-years of follow-up, 2556 patients developed T2D. The incidence rate (IR) of T2D was highest in the Left-Chemo group 11.3 (95% CI: 10.4–12.2) per 1000 person-years and lowest in the Rectal-No-Chemo group 9.6 (95% CI: 8.8–10.4). Between-group unadjusted hazard ratio (HR) of developing T2D was similar and non-significant. In the adjusted analysis, Rectal-No-Chemo was associated with lower T2D risk (HR 0.86 [95% CI 0.75–0.98]) compared to Right-No-Chemo.For all six groups, an increased level of body mass index (BMI) resulted in a nearly twofold increased risk of developing T2D.Conclusions:This study suggests that postoperative T2D screening should be prioritised in CRC survivors with overweight/obesity regardless of type of CRC treatment applied.Funding:The Novo Nordisk Foundation (NNF17SA0031406); TrygFonden (101390; 20045; 125132).