Late Adverse Effects Research Articles

Healthcare providers' expected barriers and facilitators to the implementation of person-centered long-term follow-up care for childhood cancer survivors: A PanCareFollowUp study.

Childhood cancer survivors face high risks of adverse late health effects. Long-term follow-up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high-quality long-term follow-up care, we explored expected barriers and facilitators for establishing this follow-up care among healthcare providers from four European clinics. A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi-structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long-term follow-up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long-term follow-up care results to convince hospital managers. This study identified several factors for successful implementation of long-term follow-up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors.

Transvesical open prostatectomy versus transurethral resection of the prostate for the treatment of benign prostatic hyperplasia, Iraq: A retrospective study

Background and Objective: Surgical treatment is an effective option for symptomatic benign prostatic hyperplasia (BPH), after failed conservative therapy. Transurethral resection of the prostate (TURP) is considered as a standard treatment method for the management of the small to medium prostate while transvesical open prostatectomy (OP) is a standard option for great prostate. The objective of this study is to evaluate the efficacy and safety of both (B-TURP) and (OP). Methods: The present study included 73 patients underwent either transvesical open prostatectomy (31 patients) or bipolar transurethral resection of the prostate (42 patients) between May 2019 to May 2021, in Erbil-city. The baseline characteristics, intraoperative and postoperative characteristics plus early and late adverse effects were obtained from medical records for all patients in both groups, retrospectively. The data analyzed and compared statistically. Results: The baseline characteristics in the studied groups showed no significant differences except for the prostate size which was more on the OP group. According to the results, operative time was significantly (P <0.001) lower in the OP group. The means of the following variables in the OP group were significantly higher than those of the B-TURP group: Hospitalization days (P <0.001), days of catheter removal, back to normal activity (P <0.001), QoL score (P = 0.027), Qmax (P < 0.001), and PVR (P = 0.046), while no significant difference was detected regarding IPSS (P = 0.404). Conclusion: B-TURP was superior to OP regarding the hospitalization days, recovery time back to normal day-activity, and quality of life. Otherwise, both mentioned approaches work well for the treating symptomatic BPH.

Patient selection, ventricular tachycardia substrate delineation and data transfer for stereotactic arrhythmia radioablation. A Clinical Consensus Statement of the European Heart Rhythm Association (EHRA) of the ESC and the Heart Rhythm Society (HRS).

Stereotactic arrythmia radioablation (STAR) is a novel, non-invasive and promising treatment option for ventricular arrythmias (VA). It has been applied in highly selected patients mainly as bail-out procedure, when (multiple) catheter-ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including etiology specific aspects, and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.

Proton Therapy in The Treatment of Head And Neck Cancers- Review.

Head and neck cancers rank as the seventh most common cancer worldwide, nearly half of which result in death. The most common treatment methods for head and neck cancers include radiotherapy and surgery. Proton therapy has emerged in radiotherapy for cases where tumors are located near anatomically sensitive areas where the radiation dose must be strictly limited. The purpose of the work is to discuss the role of the proton therapy in the treatment in various types of cancer, and particularly head and neck tumors. Proton therapy allows for the delivery of radiation doses to critical organs to be reduced, resulting in a decrease in the occurrence of late adverse effects on these organs. The occurrence of side effects caused by proton therapy depends on the relative and absolute volume of organs at risk receiving specific radiation doses. Proton therapy represents a promising alternative to conventional radiotherapy due to the reduced number of complications in healthy tissues by delivering a lower radiation dose outside the tumor area.

Early exposure to glyphosate during larval development induces late behavioural effects on adult honey bees

As the most abundant pollinator insect in crops, Apis mellifera is a sentinel species of the pollinator communities. In these ecosystems, honey bees of different ages and developmental stages are exposed to diverse agrochemicals. However, most toxicological studies analyse the immediate effects during exposure. Late effects during adulthood after early exposure to pollutants during larval development are poorly studied in bees. The herbicide glyphosate (GLY) is the most applied pesticide worldwide. GLY has been detected in honey and beebread from hives near treated crops. Alterations in growth, morphogenesis or organogenesis during pre-imaginal development could induce late adverse effects after the emergence. Previous studies have demonstrated that GLY alters honey bee development, immediately affecting survival, growth and metabolism, followed by late teratogenic effects. The present study aims to determine the late impact on the behaviour and physiology of adult bees after pre-imaginal exposure to GLY. For that, we reared brood in vitro or in the hive with sub-chronic exposure to the herbicide with the average detected concentration in hives. Then, all newly emerged bees were reared in an incubator until maturity and tested when they became nurse-aged bees. Three behavioural responses were assessed as markers of cognitive and physiological impairment. Our results show i) decreased sensitivity to sucrose regardless of the rearing procedure, ii) increased choice latency and locomotor alterations during chemotaxis and iii) impaired associative learning. These late toxicity signs could indicate adverse effects on task performance and colony efficiency.

Distressed personality is associated with late adverse effects in long-term survivors of Hodgkin lymphoma.

There are few studies of personality traits in long-term Hodgkin lymphoma survivors (HLSs) treated according to contemporary stage-and risk-adapted approaches. The Distressed Personality (DP) Scale covers negative affectivity and social inhibition. We examined differences in self-reported late adverse effects (LAEs) between HLSs with and without DP and other explanatory variables. This cross-sectional questionnaire-based study included a population-based cohort of HLSs treated from 1997 to 2006, aged 8-49 years at diagnosis, and alive in 2016. Among 518 eligible HLSs, 303 responded (58%), and 294 completed the DP scale. DP was defined by scores above cut-off on both the negative affectivity and social inhibition subscales. LAEs studied were major depression, posttraumatic stress disorder, sleep problems, obesity, neuropathy, fatigue, memory problems, and general health. DP and 10 other explanatory variables were tested against LAEs as dependent variables in multivariable regression analyses. The mean age at survey was 45.9 years (standard deviation [SD] 4.6), mean follow-up time 16.7 years (SD 3.0), and 48% were females. Eighty-two HLSs had DP (28%, 95% confidence interval 23% - 33%). All LAEs except obesity were significantly more common/had higher mean score in HLSs with DP. In multivariable analyses, presence of DP was significantly associated with all LAEs except obesity. The presence of DP is common among HLSs. The presence of DP was associated with most self-report LAEs examined. Including assessment of personality traits in the survivorship care plans of HLSs should be considered. Prospective studies assessing the influence of pretreatment DP on LAEs are warranted.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors.

FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors. Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post-treatment to evaluate treatment efficiency and adverse effects. Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression. Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT.

Intensity Modulated Carbon Ion Radiation Therapy Using Pencil Beam Scanning Technology for Patients With Unresectable Sacrococcygeal Chordoma

ObjectivesTo investigate the safety and efficacy of intensity modulated carbon ion radiotherapy (IM-CIRT) using pencil beam scanning technology for patients with unresectable sacrococcygeal chordoma (SC). Methods and MaterialsA total of 35 unresectable SC patients were retrospectively analyzed, including 54.3% (19/35) recurrent cases. 68.6% (24/35) cases’ tumor located in S2 or above, and all cases were treated with hypofractionated IM-CIRT. The median dose was 70.4 (range 69 - 80) Gy (RBE) in 16 (range 16 - 23) fractions, typically delivered over 5 fractions per week. ResultsThe 3-year OS, CSS, PFS, LRFS and DMFS rates with a median follow-up time of 42 (12∼91) months for the entire cohort were 93.2%, 96.3%, 61.8%, 80% and 77.3%, respectively. Multivariate analysis revealed that GTV volume (HR, 3.807; 95% CI: 1.044 - 13.887, p = 0.043) was the only significant prognostic factor for PFS and the dose for the GTV ≥ 70.4 Gy (RBE) was relevant with significantly better LRFS (HR, 0.190; 95% CI: 0.038 – 0.940, p = 0.042). No significant prognostic factor for OS, CSS and DMFS and no severe (i.e., grade ≥ 3) acute toxicity were identified. Severe late toxicities occurred in 3 patients (8.57 %): pain (1 patient), motor neuropathy (1 patient) and skin ulcer (1 patient). Furthermore, no severe toxicity related to urinary function or defecation was observed following IM-CIRT. Pain grades improved or remained unchanged in 85.7% of patients. ConclusionIM-CIRT produced acceptable 3-year outcomes without substantial late adverse effects, especially urinary and anorectal complications for SC, and did not appear to increase pain. IM-CIRT at high doses using hypofractionated RT may improve outcomes for local control and seems to be feasible even for postoperative recurrent SC.

How to treat advanced Hodgkin lymphoma?

In this review, we analyzed the different therapy options in patients with advanced Hodgkin lymphoma (HL). The treatment of advanced HL has greatly evolved during the last decade even still based on polychemotherapy. Mature data established that the better strategies require Positron emission tomography (PET)-driven treatments which allow to optimize the balance between disease control and both immediate and late treatment adverse effects, leading to cure most patients while minimizing the risk of toxicity. Indeed, PET-driven deescalated strategies offer the better treatment option. The recent incorporation of targeted therapies, anti-CD30 or anti-programmed cell death protein 1 (PD1) in combination with chemotherapy should quickly change the game and be a step forward to still decrease the risk of treatment toxicity and improve the cure rate. The standard of care for advanced HL remains currently PET-driven chemotherapy and should rapidly evolve with the addition of targeted therapy combined with chemotherapy.

Phase II Clinical Trial of Second Course of Stereotactic Body Radiotherapy for Spinal Metastases

Purpose: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. Methods: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. Results: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6–51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1–2 and S1–5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. Conclusions: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.

Late Urinary Toxicity After Extreme or Moderate Hypofractionated Prostate Radiation Therapy in Patients With Prior Transurethral Resection of Prostate

PurposeTo study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiotherapy. MethodsPatients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity modulated radiotherapy (MHRT or SBRT), were included in this study. Severity and duration of urinary symptoms observed during serial follow up after at least three months from radiotherapy were graded per CTCAE v5.0 using information from prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analysed with univariable and multivariable binary logistic regression. ResultsTotal 203 eligible patients were included (MHRT=114, 64-68Gy/25#; SBRT=89, 35-37.5Gy/5#). Median time from TURP to radiotherapy was 10 months (IQR 7-16), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17cc (IQR 0.5-1.35), while in MHRT and SBRT groups was 1.03 cc (IQR 0.4-1.15) and 1.27 cc (IQR 0.5-1.4), respectively. At a median follow up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n=17) and 23.2% (n=47) respectively. Grade 3 symptoms were observed at median 29 months (IQR 19-62) after radiotherapy completion, lasting for a median duration of 8 months (IQR 2-14). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiotherapy, fraction size, prostate volume, TURP to radiotherapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. Conclusion: In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiotherapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiotherapy.

Testicular cancer survivorship program at National Cancer Institute in Slovakia.

e13792 Background: Testicular germ cell tumors (GCTs) are highly curable malignancies. Survivors of GCTs represent a growing population with a long life expectancy after curative cancer treatment. GCT survivors may experience a variety of late adverse effects of treatment and reduced quality of life. Therefore, National Cancer Institute in Slovakia has developed a testicular cancer survivorship program with a long-term follow-up of GCT survivors aiming to evaluate late toxicities and their underlying molecular mechanisms. Methods: The long-term annual follow-up of GCT survivors is established per our institutional guidelines for testicular cancer survivorship program. GCT survivors are referred to our testicular survivorship outpatient clinic at least 5 years after completion of curative treatment, and are followed annually throughout their lives. During each visit, patient’s history is updated, physical examination is performed, blood and urine samples are collected, and survivors complete validated questionnaires for evaluation of late toxicities (peripheral neuropathy, sexual dysfunction, cognitive impairment) and quality of life. Complete blood count, metabolic panel, lipid panel, levels of serum tumor markers, testosterone, luteinizing hormone and follicle stimulating hormone are measured at each visit. Plasma aliquots and urine samples from every visit are prospectively collected and stored in the biobank of our Translational Research Unit. Data including age, medical history, histological type, stage, prognostic group, type of treatment, laboratory values, and questionnaire scores are collected and recorded in our electronic survivorship database. In addition, information on important survivorship topics is provided and healthy lifestyle changes are suggested to all survivors. Results: From August 2015 to January 2024 our testicular survivorship outpatient clinic performed 1733 follow-up visits in 407 GCT survivors treated at our institution from 1984 to 2019. Median age at the first follow-up visit at the survivorship clinic was 41 years (range 21 - 77). Median time from the curative treatment to the first follow-up visit at the survivorship clinic was 7 years (range 4 - 32). To date, 104 patients have had at least 7 follow-ups. Eighty-six (21.13 %) patients were treated with surgery only, 278 (68.3 %) with chemotherapy, 28 (6.88 %) with radiotherapy, and 15 (3.69 %) patients with both chemotherapy and radiotherapy. To date, 18 publications (including papers and abstracts) have been published using the data from our testicular survivorship database. Conclusions: Testicular cancer survivorship program with the long-term annual follow-up of GCT survivors has been established at National Cancer Institute in Slovakia. The ongoing prospective study for evaluation of late toxicities and their underlying mechanisms is part of the program. Our large database offers valuable data for the future research.

Long-term (11 Years) Results of Laparoscopic Gastric Bypass: Changes in Weight, Blood Levels of Sugar and Lipids, and Late Adverse Effects : Laparoscopic Gastric Bypass Results.

Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) remains the most effective procedure to treat severe obesity with proven short- and intermediate-term benefits. The main goal is to describe the effects on weight and biochemical laboratory tests after long-term follow-up (11 years). A prospective cohort of adults with obesity treated with LRYGB between 2004 and 2010 in one center were studied. Patients with prior bariatric or upper digestive tract surgery, hiatal hernia >4 cm, alcoholism, or decompensated conditions were excluded. The study enrolled 123 patients, with a mean follow-up of 133±29 months and a 14% loss of participants. The percentage of Total Weight Loss (%TWL) at one, five, and eleven years was 30.3±8.4%, 29.1±6.9%, and 23.4±7%, respectively. Of the patients, 61.3% (65/106) maintained a %TWL≥20 after eleven years. Recurrent Weight Gain (RWG) at five and eleven years was 2.6±11.4% and 11 ±11.5%, respectively. At the end of the follow-up, 31.1% (33/106) of patients had RWG≥15%. Hypercholesterolemia and hypertriglyceridemia improved in 85.7% (54/63) and 90.2% (7/61) of the cohort, respectively. Remission of diabetes occurred in 80% of this subgroup. Gallstones developed in 28% of patients, and bowel obstruction due to internal hernia occurred in 9.4%. Anemia due to iron deficiency appeared in 25 patients. After surgery, there is a significant and durable loss of weight, with a tendency for late Recurrent Weight Gain. Furthermore, the improvement in biochemical parameters is sustained over time, but surgery's adverse effects may appear later.

Therapeutic Doses of Antioxidants Inhibit the Growth and Enhance the Effects Chemotherapy and Radiation Therapy on Cancer Cells by Blocking the Uptake and Metabolism of Glucose and Glutamine

Chemotherapy and radiation therapy have produced increased 5-year survival rate in majority of cancers; however, acute side-effects during treatment and late adverse effects after these therapies remain a major concern of oncologists. To improve further 5-year survival rate and reduce acute and late adverse effects of therapies, a new non-toxic biological approach is needed. Experimental data for such an approach was available for over 25 years. For example, therapeutic doses of antioxidants inhibit the growth of cancer cells and enhances the growth-inhibitory effects of chemotherapeutic agents and x-irradiation on cancer cells but not on normal cells. These exciting observations failed to draw any attention from oncologists, because mechanistic data on therapeutic doses was not available until now. The mechanistic data on preventive doses of antioxidants suggested that they scavenge free radicals. Since one of the mechanisms of action of chemotherapy and radiation therapy on cancer cells is mediated by free radicals, oncologists fear that supplementation with antioxidants may reduce the effectiveness of cancer therapies by neutralizing free radicals. Cancer cells require glucose and glutamine for their survival and proliferation. This review briefly describes the effects of therapeutic doses of antioxidants alone and in combination with chemotherapy and radiation therapy on the growth of neoplastic cells and normal cells. It also presents evidence to show that such doses of antioxidants reduce the uptake and metabolism of glucose and glutamine in cancer cells. We propose that therapeutic doses of multiple antioxidants can selectively kill cancer cells and enhance the growth-inhibitory effects of therapeutic agents on cancer cells without affecting normal cells by inhibiting the uptake and metabolism of glucose and glutamine.

Protocol for the 'Supporting Young Cancer Survivors who Smoke' study (PRISM): Informing the development of a smoking cessation intervention for childhood, adolescent and young adult cancer survivors in England.

Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking. The PRISM study aims to undertake multi-method formative research to explore the need for, and if appropriate, inform the future development of an evidence-based and theory-informed tobacco smoking cessation intervention for CAYA cancer survivors. PRISM involves three phases of: 1) an environmental scan using multiple strategies to identify and examine a) smoking cessation interventions for CAYA cancer survivors that are published in the international literature and b) current smoking cessation services in England that may be available to, or tailorable to, CAYA cancer survivors; 2) a qualitative study involving semi-structured interviews with CAYA cancer survivors (aged 16-29 years and who are current or recent ex-smokers and/or current vapers) to explore their views and experiences of smoking, smoking cessation and vaping; and 3) stakeholder workshops with survivors, healthcare professionals and other stakeholders to consider the potential for a smoking cessation intervention for CAYA cancer survivors and what such an intervention would need to target and change. Findings will be disseminated to patient groups, healthcare professionals and researchers, through conference presentations, journal papers, plain English summaries and social media. PRISM will explore current delivery of, perceived need for, and barriers and facilitators to, smoking cessation advice and support to CAYA cancer survivors from the perspective of both survivors and healthcare professionals. A key strength of PRISM is the user involvement throughout the study and the additional exploration of survivors' views on vaping, a behaviour which often co-occurs with smoking. PRISM is the first step in the development of a person-centred, evidence- and theory-based smoking cessation intervention for CAYA cancer survivors who smoke, which if effective, will reduce morbidity and mortality in the CAYA cancer survivor population.

Late Adverse Effects after Treatment for Childhood Acute Leukemia.

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. CONCLUSION: It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.

Frequency of Complete Remission With R-CHOP Therapy in Patients With Diffuse Large B Cell Lymphoma.

Background Diffuse large B-cell lymphoma (DLBCL) exhibits notable heterogeneity in clinical presentations and treatment responses, posing challenges in predicting outcomes and tailoring therapeutic strategies for affected patients. Despite advancements in molecular subtyping and prognostic assessment, uncertainties persist regarding the optimal management of DLBCL, highlighting the need for localized investigations to better understand treatment responses and outcomes within specific patient populations. Objective To assess the frequency of complete remission (CR) in diffuse large B-cell lymphoma (DLBCL) patients undergoing first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy within a specific adult population. Material and methods This descriptive study was conducted within the Department of Oncology Hayatabad Medical Complex, Peshawar, Pakistan from August 8, 2022, to April 8, 2023. The study included newly diagnosed DLBCL patients aged 20-70 years, excluding those who had received prior treatment. There were 55 (57.9%) males and 40 (42.1%) females. Data on demographic characteristics, disease duration, and CR outcomes were collected using a predefined data collection form. Results The majority of patients (80, 84.2%) achieved CR following R-CHOP therapy. In terms of age distribution, 43 (45.3%) patients were aged ≤45 years, while the remaining belonged to the >45 years age group. The duration of the disease was ≤ 3 months in 60 (63.2%) cases, whereas it exceeded three months in 35 (36.8%) cases. With regards to BMI classification, nine (9.5%) patients had a BMI < 18.5 kg/m2, 49 (51.6%) fell within the range of 18.5-24.9 kg/m2, and the remaining 37 (38.9%) patients had a BMI between 25-30 kg/m2. Conclusion Diffuse large B-cell lymphoma (DLBCL) remains a heterogeneous disease entity with variable clinical outcomes. While R-CHOP therapy demonstrates promising efficacy in achieving CR, concerns regarding late adverse effects persist. Addressing these challenges requires continued research efforts to validate novel prognostic markers and develop alternative treatment approaches, ultimately improving patient outcomes and reducing the global burden of DLBCL.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial

PurposeThe POP-RT phase III randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT) for high/very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. Materials/MethodsLate urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65Gy, V68Gy) in the approved radiotherapy plans was compared for urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. ResultsComplete combined data for late urinary symptoms and dosimetry was available for 193/224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for WPRT and PORT (5.2% vs 4.1%, p=0.49), while grade 2 toxicity was 31.3% vs 22.7% respectively (p=0.12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior TURP, grade 2+ acute urinary toxicity, low bladder dose (V10Gy) and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. ConclusionOver long term follow up, whole pelvic radiotherapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiotherapy. The long term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

The impact of XPC gene single nucleotide polymorphism rs2228001 on head and neck cancer patients' response to radiotherapy treatment.

Head and neck squamous carcinoma (HNSC) is the sixth most common neoplasm, with a 40-50% overall survival rate. HNSC standard treatment depends on tumor size, metastasis or human papillomavirus (HPV) status including surgery, chemotherapy, and radiotherapy. The last two may lead to defects in the tumor microenvironment and cancer cell biology as disorders in DNA damage repair systems. Here, we evaluate the correlation between single nucleotide polymorphism (SNP) rs2228001 in the XPC gene with the early and late adverse effects of radiotherapy, determine the distribution of the SNP and post-treatment follow-up in HNSC patients. Head and neck cancer tissues and clinical data were obtained from 79 patients. The SNP of the XPC gene (rs2228001) was evaluated with polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). The chi-square test was used to determine the correlation between mutation and adverse effects occurrence. Single nucleotide polymorphism rs2228001 in the XPC gene is correlated with the early adverse effect of skin reaction and the late adverse effect of elevated C-reactive protein (CRP) levels in the HNSC patients.