Completion Of Adjuvant Treatment Research Articles

Differential impact of incrementally elevated CA 19-9 levels on prognosis of resected pancreatic ductal adenocarcinoma

BackgroundCA 19–9 is an extremely useful biomarker for pancreatic ductal adenocarcinomas (PDACs). However, the optimal cut-off and prognostic significance at higher cut-offs are yet to be determined. MethodsRetrospective analysis included patients with PDAC who underwent curative resection from January 2010 to May 2020 at Tata Memorial Centre, Mumbai. The pretherapy CA 19–9 was dichotomized using various cut-off levels and analysed. ResultsIn 244 included patients, the median overall survival (OS) for those with CA19-9 level (IU/ml) < or >78, 200, 500, 1000, and 2000 was 27, 24, 23, 22, 21 months versus 18, 16, 15, 14, 13 months; respectively, and was statistically significant (p-value- 0.002, 0.001, 0.002, 0.002 and 0.004, respectively). The number of recurrences and mortality had significant correlation with CA 19–9 cut-offs. On multivariate analysis, adjuvant treatment completion (p-0.004) and decreasing or stable CA19-9 after Neoadjuvant therapy (NAT) (p- 0.031) were associated with improved OS. ConclusionThe prognostic significance of CA 19–9 was observed at all the cut-off levels examined, beyond mere elevated value as per the standard cut-off level. In patients with high CA19-9 level, surgery should be offered if technically and conditionally feasible, only when a response in CA19-9 level to NAT is achieved.

Fate of de-functioning ileostomy after left colon and rectal cancer resection: observation from a single unit of a cancer hospital.

Background: De-functioning ileostomy (DS) has been shown to reduce rate of anastomotic leak after left colon and rectal cancer resection and can avoid consequences of leak with its morbidity and possible mortality. Externalisation of bowel is not easily appreciated; patients always inquire about the timing of closure and not all stomas are closed. The aim of the study is to assess the timing of stoma closure and the reasons for stoma becoming permanent. Methods: Patients who underwent surgery for left colon and rectal cancer with de-functioning stoma from April 2019 to May 2022 in single unit of Bhaktapur Cancer Hospital, were assessed regarding timing of stoma closure. We have made a policy of stoma closure after completion of adjuvant therapy. De-functioning stoma that was not reversed at follow up were assessed regarding reason for it becoming permanent. Results: Forty-two patients underwent de-functioning stoma during the study period; 30 after rectal resection, 2 after pouch creation, 6 after anterior resection and 4 after left hemicolectomy. Twenty-eight (77%) stomas were closed, 5 are receiving adjuvant treatment. Closure was not done in 8 patients; 5 due to recurrence of disease; 1 due to patient wish, 2 deaths occurred prior to closure, one due to COVID-19 and another due to acute myocardial infraction. One patient with multiorgan resection died within 30 days of surgery due to other medical cause. The median time of stoma closure after completion of adjuvant treatment is 8 weeks, IQR (7-10). Patients had to stay with stoma for a median period of 6months, IQR (5-8). The median time for discharge after stoma reversal is 9 days, IQR (7-10). There were 4 Grade II Clavien-Dindo complications after stoma closure. Conclusion: Seventy- seven percent of patients with DS underwent closure in our series. Recurrence was the most common cause for it becoming permanent.

Fertility-sparing approach to malignant ovarian germ cell tumors - Oncologic and obstetric outocome: A retrospective study.

To evaluate oncologic (such as disease-free and overall survival) and obstetric outcomes in patients diagnosed with malignant ovarian germ cell tumors (MOGCTs). Patients diagnosed with MOGCTs between March 2007 and February 2022 were evaluated and patients who underwent fertility sparing surgery were included in this retrospective study. The obstetric and oncologic outcomes were evaluated by collecting data up until the patient's last follow-up visit from the hospital records and patient files. The study was approved by Başkent University Institutional Review Board (KA23/124). Seventy FSS patients were included in this study. The median age of the patients was 22.5 years (range: 11-37). The median follow-up time was 92.0 months (10-189). Immature teratoma was the most common histological subtype (32.9%). Bilateral involvement was detected in only one patient with immature teratoma (1.4%). The 5-year DFS rates of immature teratoma, dysgerminoma, yolk sac, and mixed germ cell histologic types were 91.1%, 94.1%, 82.4%, and 88.9%, respectively (P: 0.716). The 5-year OS rates of the same histologic types were 95.7%, 100%, 88.2%, and 88.9%, respectively (P = 0.487). All patients (100%) had a regular menstrual cycle after the completion of adjuvant treatment. The mean time between the last chemotherapy and menstruation was 4.38 months. To date, a total of 34 patients tried to conceive after the completion of disease treatment. A total of 23 (67.6%) patients conceived, resulting in 27 live births in 22 (100%) patients. Fertility preservation should be the first treatment option in MOGCTs in young patients due to the unilateral involvement of the disease and its chemosensitive nature.

Abstract B021: Breast cancer survivors and expression of p16INK4a, DNA damage, and the SASP prior to and following treatment

Abstract Purpose: To examine whether breast cancer therapy accelerates aging via increasing expression of cellular senescence (p16INK4a), the DNA damage response (DDR), or the proinflammatory senescence associated secretory phenotype (SASP), we measured gene expression of these pathways in a cohort of women recruited following a diagnosis of breast cancer (Stage 0-III). Methods: The RISE study is a Los Angeles-based longitudinal, observational study of biological and behavioral processes following surgery, radiation (RT) and/or chemotherapy (CT); and more persistent changes in these processes in the months after adjuvant treatment completion and initiation of endocrine therapy (6, 12, 18 month post-treatment follow-ups). Of the 270 women enrolled in the study, gene expression data was available for 184 women (aged average of 55.5 years, SD 11.2). Peripheral blood mononuclear cells (PBMC) gene expression was determined using RNA sequencing on quality-verified RNA. We determined transcript abundance for cellular senescence marker p16INK4a, genes that express proteins of the SASP, and genes responsive to DNA damage. Longitudinal data for p16INK4a, DDR and SASP were modeled using mixed models, including a quadratic term for time and its interaction with four treatment groups (1: Surgery alone [no RT or CT], RT alone, CT alone, and CT+RT), and a zero-inflated two-part model with p16INK4a. Covariates included age, BMI, race, initial surgery type, receipt of interim surgery, and endocrine therapy. Results: Analyses testing whether there was a change in p16INK4a over time by treatment group revealed that all groups experienced increases in p16INK4a expression over time. At baseline 53% of women had no detectable p16INK4a transcripts in their PBMC samples, and this proportion changed over time across all groups indicating significant increases in women expressing the marker for cellular senescence, p&amp;lt;0.0001. Women receiving CT or CT+RT had a 40% and 36% increase in percentage expressing p16INK4a (26% increase among those with surgery alone and 31% for RT alone) by 18 months post treatment compared to their pretreatment values. Analyses found a significant initial increase in DDR over time in all groups (p's&amp;lt;0.002) followed by a deceleration in all three groups except CT+RT, which continued an upward trajectory. There were also significant increases in SASP across all groups (p’s&amp;lt;0.05), with a significant quadratic effect in the RT group only (p&amp;lt;0.001). Conclusions: These results indicate that there was activation of genes associated with acceleration of biological aging across all groups after breast cancer diagnosis. Survivors had increases in p16INK4a, DNA damage response genes, and SASP from pre to 18 months post treatment for breast cancer. (NCI R01 CA237535) Citation Format: Judith E. Carroll, Catherine M. Crespi, Laura Petersen, Julie E. Bower. Breast cancer survivors and expression of p16INK4a, DNA damage, and the SASP prior to and following treatment [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B021.

Shoulder recovery for head and neck cancer patients after unilateral neck dissection: a pilot exploratory study

An established side-effect of neck dissection (ND) for head and neck (HNC) tumour management includes shoulder dysfunction (SD), which can impact quality of life (QOL). Shoulder strength and range of movement (ROM) are key parameters to be monitored in SD. However, such evaluations are not routinely conducted in the clinical setting. The aim of this study was to evaluate objectively the impact of ND on shoulder functions. Methods: This is a pilot exploratory study in a tertiary cancer centre. Five participants with unilateral ND and advanced HNC, completed the study. Outcome measures consisted of self-reported QOL questionnaires, C2–T1 dermatomes and shoulder ROM and strength testing. Data was collected at baseline, 1.5-months after surgery and 6-months after diagnosis (after adjuvant treatment completion). Results: Most outcome measures on the surgically affected side were negatively impacted post-operatively, with varied recovery seen at follow-up. Sensory loss was noted at C3–4 dermatome levels. Shoulder ROM and strength was reduced on the surficial side for all participants, with some recovery after six months except for two participants. Conclusion: Results of SD after ND are diverse and unique to each patient. Findings from this pilot study indicate that regular rehabilitation/exercise may facilitate recovery of shoulder function post HNC surgery. However, customised rehabilitation may yield better outcomes. Future studies with a larger sample are indicated to validate the findings of this study.

P17.08.B Single institutional retrospective review of re-irradiation in High Grade Gliomas in a tertiary UK centre

Abstract Background Recurrent high grade gliomas (HGG) pose a treatment challenge as no definite guidelines exist. Re-excision could be appropriate in some cases while systemic therapy options are only a handful. We thus need to resort to the option of re-irradiation at some point but there could be a wide variety of techniques, volumes &amp; doses to choose from due to lack of robust evidence. The UK wide BRIOCHe study for Glioblastoma Multiforme (GBM) will help in providing some standardisation. With this retrospective study, we aim to review our institutional practice with re-irradiation &amp; our patient outcomes. Material and Methods Electronic health records over a period of 3 years from 1 Jun 2019 to 30 May 2021 were searched for patients with HGG that underwent a course of re-irradiation. Various patient factors, tumour &amp; treatment factors at baseline and at recurrence and survival data were collected. Results Total of 8 patients received re-irradiation with all except one having a performance status of 1 at the time of treatment. Seven patients had GBM, one had transformation from baseline G2 glioma and the eighth patient had anaplastic oligodendroglioma (ODG). MGMT was methylated in 62.5% patients while IDH mutation was present only in the transformed glioma. Majority patients had radiotherapy dose of 60Gy/30 fractions with concurrent temozolomide (TMZ) at baseline to a median CTV volume of 186cc. A median of 6 cycles of TMZ were given in the adjuvant setting. Median time to recurrence from completion of adjuvant treatment was 6.7 months (range: 0.9 - 171.6 months). Most recurrences were in the same or an adjacent lobe whereas 1 patient had a multi-focal recurrence. Half the patients at recurrence underwent a re-resection. All patients had salvage chemotherapy at the time of recurrence with a median of 2 regimens and a median of 6 cycles prior to re-irradiation. All patients received a re-irradiation dose of 35Gy in 10 fractions to a median CTV volume of 149cc. The median interval from previous radiotherapy was 18.9 months (range: 11.6 - 190.5 months). The median time to progression from re-RT was 5.4 months (CI: 3.4 - 7.4) and median survival from re-RT was 7 months (CI: 6.2 - 7.8). The median overall survival since diagnosis was 35.1 months (CI: 22.2 - 48.1), one patient was lost to follow up. Conclusion Re-irradiation is a safe &amp; feasible treatment option in carefully selected cases of high grade glioma.

Single-arm phase II trial of carboplatin and mirvetuximab soravtansine as neoadjuvant chemotherapy (NACT) for advanced- stage ovarian, fallopian tube or primary peritoneal cancer (EOC) who are folate receptor α positive (NCT04606914) (578)

Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria. Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria.

Germline BRCA mutations are associated with an increased likelihood of secondary cytoreductive surgery in ovarian cancer patients (116)

<b>Objectives:</b> <i>BRCA</i> mutations have been associated with improved outcomes in ovarian cancer patients, specifically with delayed recurrences. This study aimed to compare the secondary cytoreduction rates and eligibility among ovarian cancer patients by <i>BRCA</i> mutation status. <b>Methods:</b> The study was retrospective and included high-grade serous ovarian cancer patients from one Canadian center and two Israeli centers from January 1999 to December 2018, with the first disease recurrence 12 months or more from the last cycle of platinum-based chemotherapy. Demographic and genetic data, tumor characteristics, pattern of recurrence, and surgical and medical treatments were obtained from electronic charts. Eligibility for secondary cytoreduction was defined as recurrence 12 months or longer from completion of adjuvant treatment, up to three lesions at recurrence, and absence of ascites, in line with DESKTOP criteria. Patients were grouped according to <i>BRCA</i> mutation status. Continuous variables were compared using the student's t-test and categorical variables using the Chi-square test. Regression analysis was used to identify predictors of eligibility for and performance of secondary cytoreduction. <b>Results:</b> One hundred forty-seven patients were enrolled, including 97 from Canada and 50 from Israel. Forty-seven patients (32%) had a <b>Conclusions:</b> Germline <i>BRCA</i> mutation carriers are more likely to undergo secondary cytoreduction, most likely due to lower volume disease at recurrence. This observation should be considered when planning the follow-up for these patients after first-line treatment.

The impact of frailty on adjuvant treatment in patients with head and neck free flap reconstruction—A retrospective study using two independent frailty scores

ObjectivesReconstructive surgery may result in prolonged postoperative recovery, especially in frail patients, which in turn may impact delivery of adjuvant therapy. To date, no studies have investigated potential associations between frailty and adjuvant treatment delivery after reconstructive surgery. We examine the impact of frailty on time to initiation, duration, and completion of adjuvant treatment after reconstructive surgery for head and neck cancers (HNCs). MethodsA retrospective review of patients who underwent free flap reconstruction for HNC at a single institution from 2015 to 2021 and received adjuvant radiation was performed. Frailty was assessed using two independent scales: the 11-item modified frailty index (mFI) score and binary Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator. Timely adjuvant initiation (within six weeks of surgery), duration of adjuvant treatment, and completion were compared between frail and non-frail patients. ResultsOf the 163 patients included for analysis, 52 (31.9%) were identified as frail by the ACG indicator and 24 (14.7%) were identified as frail with an mFI score ≥ 3. Frail patients (mFI score ≥ 3) were significantly less likely than non-frail patients to initiate adjuvant treatment within six weeks (OR:0.21, CI:0.04–0.85, p = 0.046). Frailty designated by either frailty scale was not significantly associated with adjuvant treatment duration. Likelihood of adjuvant treatment completion was significantly lower for frail compared to non-frail patients by both scales: ACG indicator (OR 0.02, CI:9.05 × 10−4–0.25, p = 0.007) and mFI score ≥ 3 (OR:0.01, CI:6.85 × 10−4–0.13, p = 0.007). ConclusionsFrailty is associated with decreased likelihood of timely adjuvant treatment initiation and completion in patients with HNCs after free flap reconstruction.

Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker?

The aim of this study is to analyze the role of neutrophil-lymphocyte ratio (NLR) and its variation pre- and postoperatively (delta NLR) in the overall survival after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) at a single center and to identify factors associated with overall survival. A retrospective study of consecutive patients undergoing pancreatectomy due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between the evaluated factors and overall survival was analyzed using a log-rank test and Cox proportional hazard regression model. Overall, 242 patients underwent pancreatectomy for PDAC or undifferentiated carcinoma. OS was 22.8months (95% confidence interval (CI): 19.5-29), and survival rates at 1, 3, and 5years were 72%, 32.5%, and 20.8%, respectively. NLR and delta NLR were not significantly associated with survival (hazard ratio (HR) = 1.14, 95%CI: 0.77-1.68, p = 0.5). Lymph node ratio was significantly associated (HR = 1.66, 95%CI: 1.21-2.26, p = 0.001) in the bivariate analysis. In multivariable analysis, the only factors that were significantly associated with survival were perineural invasion (HR = 1.94, 95%CI: 1.21-3.14, p = 0.006), surgical margin (HR = 1.83, 95%CI: 1.10-3.02, p = 0.019), tumor size (HR = 1.01, 95%CI: 1.003-1.027, p = 0.16), postoperative CA 19-9 level (HR = 1.001, p < 0.001), and completion of adjuvant treatment (HR = 0.53, 95%CI: 0.35-0.8, p = 0.002). Neutrophil-lymphocyte ratio and delta NLR were not associated with the overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level, and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.

Fear of Cancer Recurrence and Sleep in Couples Coping With Early-Stage Breast Cancer.

Fear of cancer recurrence (FCR) and sleep disturbance are common in cancer survivors. Yet, little research has examined their relationship, and even less is known about what links may exist between these variables among the intimate partners of cancer survivors. This study examines the relationship between FCR and sleep disturbance in breast cancer survivors and their partners. Using daily sleep data collected at two distinct periods early in survivorship-the completion of adjuvant treatment and the first post-treatment mammogram-higher survivor and partner FCR was hypothesized to predict greater sleep disturbance. Breast cancer survivors and intimate partners (N = 76 couples; 152 individuals) each reported sleep duration, sleep quality, sleep onset latency, and wake after sleep onset each morning of two 21-day sleep diary bursts during the first year post-diagnosis. Three validated measures formed latent FCR factors for survivors and partners, which were used to predict average daily sleep. Across both sleep diary bursts, survivor FCR was associated with their own reduced sleep duration, reduced sleep quality, and greater sleep onset latency. Survivor FCR was also associated with their partners' reduced sleep quality and greater sleep onset latency. Partner FCR was associated with their own reduced sleep duration, reduced sleep quality, and greater sleep onset latency. Partner FCR was also associated with survivors' reduced sleep quality. Findings revealed intrapersonal and interpersonal associations between FCR and sleep disturbance, addressing gaps in knowledge on FCR and an outcome with known short- and long-term implications for health and mortality.

The Effect of the Presence of a Surgical Oncologist on Access to Surgery

Background: Surgical oncology needs continue to grow as cancer prevalence increases. Recent research has highlighted the disparity in cancer care that can occur due to physical and resource-related barriers. Rural patients are less likely to receive care that is on par with current standards due to geographic distances that must be traveled to receive appropriate care. Methods: Chart review was conducted of patients newly diagnosed with a resectable stage I-III pancreatic, gastric, or hepatic cancer or sarcoma during the employment of a surgical oncologist at our community hospital with a period during which there was no such specialist. By comparing percentage of treatment completion, wait times, completion of adjuvant treatment, and patient outcomes, a link between access and outcomes can be identified. Results: From 12/23/16 to 3/31/18, when no surgical oncologist was employed (Group A), 66 of 123 eligible patients received surgery (53.66%). In contrast, from 4/1/18 to 4/1/20, when a surgical oncologist was employed (Group B), 119 of 192 eligible patients received surgery (61.98%). Chi squared analysis with respect to tumor stage, with non-staged patients classified into a unique stage, demonstrated no statistically significant difference with a p-value of 0.1178, suggesting that the demonstrated increase in surgery completion is not due to differences in tumor stage. Conclusion: Preliminary analysis demonstrates the presence of a surgical oncology specialist plays a significant role in cancer care outcomes. Further research will be performed to identify other factors such as surgery wait time, completion of neoadjuvant and adjuvant therapy, and overall patient outcomes.

Comparison of Functional and Survival Outcomes in Pedicled and Microsurgical Flap Reconstruction for Near-Total and Total Glossectomies.

Introduction:Patients with advanced carcinoma tongue end up with near-total/total glossectomy (NTG/TG). We intended to compare functional, oncological, and survival outcomes of patients undergoing pedicled and microsurgical flap reconstruction in NTG/TG patients at our hospital.Methodology:A prospective study was conducted for 7 years on 91 patients with carcinoma tongue who underwent NTG/TG at our institute. Patients underwent anterolateral thigh (ALT), free radial artery forearm flap (FRAFF), and pectoralis major myocutaneous (PMMC) flap reconstruction and were followed up for immediate complications and functional outcomes for speech, swallowing, and decannulation after completion of adjuvant treatment and then for survival rates for a period of 60 months and statistically analysed with log rank test and Fisher’s exact test for correlation.Results:Ninety-one (42.85%) patients underwent NTG, while 57.14% underwent TG. 85% of patients had >5 mm margin, 14% had ≤ of 5 mm, and none were positive. 57% of patients did not have postoperative complications and 10% underwent re-exploration. During follow-up, 85.7% of patients were able to take orally: 52% soft diet and 32% liquid diet. Multivariate analysis of individual flaps, swallowing, and speech intelligibility values were significant. After 5 years of postadjuvant therapy, there was 76% overall survival, 11% local recurrence and 12% had regional recurrence.Discussion:Morbidity and functional outcome depends on the extent of resection. PMMC flaps can be done on lack of expertise. FRAFF has better functional outcomes owing to pliability of flap. ALT and other bulky flaps require expertise and are prone to flap-related complications. Planning of reconstruction should be based on the defect size together with counseling of patients regarding the risk of complications and delay in adjuvant therapy.

Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer

BackgroundThe incidence of colorectal cancer (CRC) in individuals of fertile age is increasing. Oxaliplatin is a cornerstone treatment in the adjuvant setting for stage III and high-risk stage II CRC. Limited data exist on possible side effects of oxaliplatin on fertility and gonadal function. More data is needed to guide possible fertility preservation procedures and aid evidence-based fertility counselling. Patients and methodsThe aim of this study (EudraCT2006-002832-10) was to prospectively investigate sex hormones and sperm parameters after oxaliplatin-based adjuvant chemotherapy to clarify the risk of infertility and hypogonadism. Twenty males aged ≤55 years and 16 females aged ≤40 years were recruited from five hospitals in the Nordic countries. All had undergone radical surgery due to CRC and were given adjuvant oxaliplatin in combination with 5-fluorouracil. Measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and semen analysis were done in males, while LH, FSH and oestradiol were measured in females. Measurements were done prior to chemotherapy, after completion of adjuvant treatment and at follow-up 1 and up to 5 years after end of treatment. ResultsFSH and testosterone levels increased in males after chemotherapy treatment but were restored at follow-up. No patients developed hypogonadism. There was a trend towards a decrease in sperm concentration during treatment (p = 0.063). When comparing sperm concentration and rapid progressive motility of sperms prior to chemotherapy and at follow-up, there were no differences, and no patients became permanently azoospermic by treatment. No distinct altering of gonadal function could be observed in females. ConclusionsOxaliplatin in combination with 5-fluorouracil seems to induce transient decrease in sperm concentration with recovery and a minor transient increase in FSH in males. No distinct altering of gonadal function was observed in females. The risk of infertility and hypogonadism in males and females after adjuvant oxaliplatin-based chemotherapy seems low.

Better survival associated with successful vitamin D supplementation in non-metastatic breast cancer survivors

Abstract Background We aimed to clarify whether successful vitamin D supplementation could predict improved survival in breast cancer (BC) survivors after completion of adjuvant treatment. Materials and Methods Patients were classified into four groups based on changes of 25(OH)D level during the treatment follow-up. Log-rank statistics were used to compare survival distributions among groups. ORs and 95% CIs were given for mortality ratios. Results The risk of death in group II with low 25(OH)D levels was 4.2 times higher than in group I with high 25(OH)D levels. (OR = 4.17 (95% CI = 1.46–11.91), P = 0.008) and the risk of death in group IV whose 25(OH)D levels never increased was 4.3 times higher (OR = 4.29 (95% CI = 1.13–16.3)). According to the log-rank test, life expectancy was significantly higher in group II compared to group I (P = 0.017) and group III (P = 0.001). Group IV had significantly lower survival times than group III (P = 0.021). Conclusions Vitamin D supplementation may play an important role in the response of the received treatments and provide a lower mortality rate and better overall -free survival (OFS) and disease-free survival (DFS) to BC patients. However, we observed a sign of poorer BC survival still after sufficient vitamin D supplementation.

174P Better survival associated with successful vitamin D supplementation in non-metastatic breast cancer survivors

Vitamin D deficiency is associated with various types of cancer, including breast cancer (BC), therefore interest has been increasing in recent years to address the role of vitamin D supplementation in cancer. Thus, we aimed to clarify whether successful vitamin D supplementation could predict improved survival in BC survivors after completion of adjuvant treatment.

Ganglionar tuberculosis infection evolving to hemophagocytic lymphohistiocytosis after anti-programmed cell death 1 treatment for high-risk melanoma: a\xa0case report

BackgroundHemophagocytic lymphohistiocytosis is a rare, potentially fatal syndrome of immune hyperactivation. Here we describe a ganglionar tuberculosis evolving to hemophagocytic lymphohistiocytosis following adjuvant immunotherapy in a melanoma patient.Case presentationA 76-year-old Caucasian male with melanoma started with fever, diffuse petechiae, splenomegaly, anemia, thrombocytopenia, hypofibrinogenemia, and hyperferritinemia 2 months following completion of adjuvant treatment with nivolumab. Positron emission tomography scan showed significant hypermetabolism in cervical, supraclavicular, mediastinal, and abdominal lymph nodes. Bone marrow aspiration demonstrated no alterations, except for a hypercellular pattern. Dexamethasone and intravenous immunoglobulin were started owing to suspicion of hemophagocytic lymphohistiocytosis. Core biopsy of the infracarinal lymph node revealed a chronic granulomatous inflammation and caseous necrosis, with positivity for Mycobacterium tuberculosis by polymerase chain reaction, and treatment for ganglionar tuberculosis was started.ConclusionThis case highlights the challenges involving programmed cell death 1 blockade in high-risk melanoma, in which infections, lymphoproliferative disorders, and sarcoidosis can mimic disease progression and trigger immune-related adverse events.

Recurrent disease in patients with stage III melanoma in the era of adjuvant immune and targeted therapy.

e21570 Background: Advancements in systemic therapy have reduced recurrence, and the adoption of nodal surveillance in place of dissection has reduced morbidity for patients with Stage III melanoma. The objective of this study was to describe the timing and pattern of recurrence in stage III melanoma patients and evaluate the impact of adjuvant treatment and nodal surveillance. Methods: A multicenter retrospective chart review of patients with pathologically confirmed Stage III cutaneous melanoma seen at either the Juravinski Cancer Centre or Walker Family Cancer Centre in Ontario, Canada from January 1, 2017 to December 31, 2019. Results: There were 137 patients with Stage III melanoma: 18% IIIA, 22% IIIB, 52% IIIC, and 8% Stage IIID as per the 8th American Joint Committee on Cancer (AJCC) 2018 staging system. 103 (75%) patients had sentinel lymph node biopsy (SLNB) only as part of initial surgical therapy, 6 (4%) had SLNB with completion dissection, and 25 (18%) had upfront radical nodal dissection. 67 (49%) patients received adjuvant therapy, of which 50 (74%) had immunotherapy, 17 (25%) received BRAF-targeted therapy, and 1 (1%) had interferon. 54 (39%) patients developed recurrent disease, with a median time to recurrence of 8.5 months (IQR: 4.3-14.9). The recurrence rates were 63% in patients who did not have adjuvant treatment and 37% in those who had adjuvant therapy, with a median time-to-recurrence of 7.5 and 9.0 months respectively. There were 30 (56%) loco-regional recurrences and 24 (44%) distant recurrences. Of the patients with loco-regional recurrence, 26 (87%) had SLNB only compared to 4 (13%) who had upfront or completion dissection. 12 (24%) patients recurred while on adjuvant treatment (7 distant recurrences and 5 loco-regional recurrences), and 8 (13%) patients recurred following completion of adjuvant treatment (5 distant recurrences and 3 loco-regional recurrences). Recurrences were detected by patients, clinicians, CT and nodal US surveillance in 43%, 20%, 28% and 9% of cases, respectively. The majority of loco-regional recurrence was detected clinically (67%) rather than by radiologic surveillance (33%). Of the 30 loco-regional recurrences, 24 underwent surgical resection of the recurrence, 4 had subsequent systemic therapy without surgery, 1 had intra-tumoral injections and 1 had no treatment. Conclusions: Recurrences in Stage III melanoma occur early, often within a year, with higher rates of loco-regional rather than distant disease. Recurrence rates were lower in those who received adjuvant therapy, but the majority of recurrences were detected by patients or clinicians, including loco-regional recurrences in patients who had SLNB only despite surveillance nodal US.

Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study.

Background: In recent years, great progress has been made in the treatment of breast cancer, but it is still one of the ten leading causes of death in women. The aim of the study was to evaluate the heparanase concentration of invasive breast cancer (IBrC) patients, before and after cancer adjuvant treatment. Methods: Eighty patients with stage IA to IIB IBrC receiving adjuvant treatment were included prospectively in this study. The heparanase concentrations were determined by an enzyme-linked immunosorbent assay. A univariate analysis was used to estimate the factors influencing the low or high pre-treatment concentration of heparanase and the low or high numerical decrease in heparanase concentration after completion of adjuvant treatment. Results: Treatment reduced the concentration of heparanase by almost four times in the general IBrC cohort. Higher levels of pre- and post-treatment heparanase were noted in oestrogen receptor-negative cancers than in positive ones. A higher post-treatment concentration of heparanase was found in patients with a triple-negative tumour compared to patients with a luminal B HER2 negative type of IBrC. Overweight IBrC subjects and those with a tumour diameter of ≥2 cm demonstrated a lower chance of a lower pre-treatment heparanase concentration. Interestingly, a pre-treatment heparanase concentration is the main predictor of the changes in heparanase concentration after adjuvant treatment. Follow-up revealed significantly lower progression-free survival (PFS) rates in IBrC patients with a pre-treatment concentration of heparanase higher than 181.46 pg/mL (PFS = 80%). Conclusions: Our findings provide supporting evidence that IBrC therapy reduced the heparanase levels, regardless of treatment patterns and a pre-treatment concentration of heparanase may serve as a prognostic indicator for future outcomes.

P130. Delayed immediate implant breast reconstruction -- how temporary is temporary?

Introduction: Subcutaneously placed breast implants for reconstruction have been associated with unsatisfactory cosmetic outcomes and high implant loss rates. In our unit they are used for skin envelope preservation to allow completion of adjuvant treatments that may negatively affect a definitive reconstruction. We noted that some patients subsequently declined definitive reconstruction. We aimed to quantify this, identify factors contributing to these decisions, and assess rates of implant loss in this group.