Radiotherapy in the Management of Non-Metastatic Inflammatory Breast Cancers: A Retrospective Observational Study

(1) Background: Inflammatory breast cancers (IBC) are characterized by a poor prognosis. This retrospective study aims to describe the clinical outcomes of non-metastatic IBC patients treated with a multidisciplinary approach with neo-adjuvant chemotherapy, surgery, and radiotherapy. (2) Methods: This single-center retrospective study included all women patients diagnosed with non-metastatic IBC between January 2010 and January 2018 at the Institut Curie (Paris, France) and treated with neoadjuvant chemotherapy, surgery, and radiotherapy. Overall survival (OS), disease-free survival (DFS), and locoregional free survival (LRRFS) were calculated from the time of diagnosis. Prognostic factors for patient survival were analyzed based on univariate and multivariate regressions. (3) Results: We identified 113 patients with a median age of 51 years. 79.7% had node-positive tumors; triple-negative breast cancers (TNBC) represented 34.6% of the cases. A large majority of patients (91.2%) received adjuvant post-mastectomy while ten patients (8.8%) received preoperative radiotherapy. Non-pathological complete response (non-pCR) was observed in 67.3% of patients. Radiotherapy delivered a median dose of 50 Gy to the breast or the chest wall in 25 fractions. With a median follow-up of 54 months, 5-year OS, DFS and LRRFS were 78% (CI: 70.1–86.8%), 68.1% (59.6–77.7%), and 85.2% (78.4–92.7%), respectively. In multivariate analysis, non-pCR was an adverse prognosis factor for OS, DFS, and LRRFS; pre-operative radiotherapy was an adverse prognosis factor for OS and DFS. Radiation-related adverse events were limited to acute skin toxicity (22% of Grade 2 and 2% of grade 3 dermatitis); no late radiation-induced toxicity was reported. (4) Conclusions: High locoregional control could be achieved with multidisciplinary management of non-metastatic IBC, suggesting the anti-tumor efficacy of radiotherapy in this rare but pejorative clinicopathological presentation. While comparing favorably with historical cohorts, OS and DFS could be potentially improved in the future with the use of new systemic treatments, such as PARP-inhibitors or immunotherapy.

Efficacy of some selected neo-adjuvant chemotherapy regimens in the treatment of advanced oral squamous cell carcinoma, and their effects on immune function

Purpose: To investigate the clinical efficacy of different neo-adjuvant chemotherapy (NACT) regimens in the treatment of advanced oral squamous cell carcinoma (OSCC), and their influence on immune function of the patients.Methods: Advanced OSCC patients (n = 94) who received NACT served as subjects in this study. They were assigned to 2 different treatment groups. Forty patients received docetaxel and fluorouracil regimen (DF group), while 54 patients received taxotere, cisplatin and fluorouracil regimen (TPF group). Surgery was performed after NACT. Changes in clinical efficacy and immune function were monitored in both groups. The clinical baseline data of patients were assessed prior to the treatments. Independent indicators of prognosis were determined using Cox regression analysis (CRA).Results: Clinical treatment efficacy was higher in TPF group than in DF group (p < 0.05). Objective remission rate (ORR) in DF group was lower than that in TPF group (p < 0.05). After chemotherapy, both groups had increased levels of CD4+ and CD4+/CD8+, and reduced level of CD8+, when compared with pre-chemotherapy values, with higher levels of CD4+ and CD4+/CD8+ ratio, and lower level of CD8+ in TPF group than in DF group (p < 0.05). Multivariate CRA revealed that the independent factors for prognosis of oral carcinoma (OC) were tumor node metastasis (TNM) stage and lymph node metastasis.Conclusion: These results indicate that TFP regimen improves clinical efficacy and immune function in patients with advanced OSCC.

Longitudinal Evolution of Cognitive Function in Colorectal and Breast Cancer Survivors Treated with (Neo)Adjuvant Chemotherapy.

Introduction & objectives: Advances in early diagnosis and treatment are improving the long-term survival of patients with cancer. Cancer-related cognitive impairment (CRCI) is often reported as a long-term chemotherapy sequel. Improving the knowledge of CRCI may help to prevent, manage and identify risk factors. Our main goal is to assess the cognitive function evolution and determine the potential influence of chemotherapy in neurological decline. Material and methods We designed a prospective and longitudinal study of a colorectal and breast cancer patient cohort (n=62) and we assessed cognitive function evolution using a battery of 11 neuropsychological tests at three time points: baseline, post chemotherapy and 6 months after finishing chemotherapy. Sociodemographic features, quality of life, anxiety and depression status were recorded as well as their interplay with cognitive evolution. Results At baseline, 14.5% of the patients had cognitive dysfunction. Older age, low level of education, colorectal cancer and comorbidities were associated to initial cognitive damage. A total of 61.9% of patients presented a decline of scores in 4 or more tests from baseline to post chemotherapy assessment. This percentage decreased to 24.4% in the late follow up evaluation, showing an intra-patient recovery after chemotherapy. Verbal and visual memory is the domain most affected. Conclusion Our data suggest that cognitive function of cancer patients treated with chemotherapy may subtly but transiently decline during treatment, with most patients recovering their cognitive function over time. Further research is needed in this field as CRCI continues to impact on quality of life and mental well-being.

P-L16 The Impact of Covid-19 on the Management of Primary and Metastatic Liver Cancers; A Single Centre Experience

Background The Covid-19 pandemic has impacted on all aspects of health care. Surgical specialties have been affected by the impact on theatre time and space, staff re-deployments, reduced ICU capacity for non-Covid patients, and in some cases this has had a significant impact on wait time for surgery and overall surgical capacity. In our tertiary referral HPB unit, the service has been relocated to two different sites throughout the pandemic. We aimed to assess the impact of this on patients undergoing liver resection Methods We examined patient data for all patients undergoing liver resection in the 15 month period prior to the introduction of national lockdown, and compared this with all patients who have undergone liver resection since. We looked at total number of cases, ICU admission rates (planned vs unplanned), length of stay, case mix, histology, rates of laparoscopic vs open surgery, and length of time from completing neoadjuvant chemotherapy to surgery. Data were obtained from electronic care records and patient notes. Results The overall number of cases was similar (84 pre-covid vs 86 since) and basic patient demographics were unaffected. Median length of stay was the same for both groups (7 days). Colorectal metastases were the underlying pathology in the majority of cases (56/84 pre Covid, 56/86 post). Numbers of laparoscopic and laparoscopic converted to open cases were reduced in the post-Covid era, 12 prior versus four since. The median time from completion of neo-adjuvant chemotherapy to surgery was also affected, increasing from 46 to 62 days. Conclusions These data show some differences in patient care in the pre and post-Covid eras, in particular a lower rate of laparoscopic surgery and longer period of time between neo-adjuvant treatment and surgery. Longer follow up is required to see if these trends persist and their effect on long term survival and recurrence rates. However, despite the strains on the system there were similar numbers of patients pre and post Covid, indicating that patients are still presenting and being treated. This showed that staff responded well to the pressures of Covid, and trainee experience would have been similar

P-OGC34 Pandemic paradigms: Early outcomes of radical chemoradiotherapy for patients with operable oesophageal and oesophago-gastric junctional adenocarcinoma

Background The peak waves of the COVID pandemic necessitated a paradigm shift in surgical management of patients with oesophageal adenocarcinoma due to both pressure on services and high mortality rates for those with COVID undergoing surgery. The Association of Upper GI Surgeons (AUGIS) guidance on treating Upper gastrointestinal cancers in the COVID era made suggestions to treat operable adenocarcinomas using definitive/consolidation chemoradiation (DCRT) over standard neo-adjuvant chemotherapy (NAC) and our unit altered practice accordingly for a cohort of patients. For affected patients we monitored and audited clinical outcomes and the initial results from this are presented here. Methods Patients with oesophageal or oesophago-gastric junctional (O/OGJ) adenocarcinoma with potentially curative disease where initial management was altered from a treatment path which would have included surgery (with or without neoadjuvant therapy) to DCRT discussed at our regional multidisciplinary team (MDT) meeting between 1st February-1st June 2020 were included. Patient demographics, investigations, treatment given and clinical outcomes were prospectively recorded. Results 31 Patients with operable adenocarcinoma of O/OGJ had treatment altered to DCRT (mean age 65.4, [range 43 – 79]), 28 (90%) Male. 1 patient deteriorated prior to starting, leaving 30 who completed DCRT. Of these 4 patients had already had NAC prior to DCRT. Follow up was for a median of 8 (range 4-8) months following start of treatment. Post- vs pre-treatment FDG-PET imaging demonstrated a significant reduction in the mean maximum standardized uptake value (SUVmax) (p = 0.003, Sign test), in all but 3 patients. 11 patients had DCRT alone, (all alive at the time of data collection), of whom 3 patients had no sign of tumour. 19 (56%) patients proceeded to salvage oesophagectomy at a median of 15(range 10-25) weeks after completion of DCRT. 42% of these patients had a complete pathological response to treatment. There was a 5% perioperative mortality rate for this group and 1 patient was found to be unresectable on the day of surgery. At the time the data was reviewed overall survival of the entire cohort was 91%, 56% of whom had no sign of residual or recurrent disease. Conclusions A disease free survival of 56% compares poorly with the literature at the 3-month interval. The long-term follow-up of these patients will only be apparent in the coming months and years. This data does not support the use of this modality in the future and alternate treatment plans should be devised for future pandemics.

Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic PIK3CA mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, such as alpelisib. The aim of this study was to evaluate the detection rate of circulating PIK3CA mutation in locally-advanced IBC (LAIBC) patients harbouring a PIK3CA mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel. PIK3CA mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a PIK3CA mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating PIK3CA mutations were found in 6/11 (55%). Among the 41 patients without PIK3CA mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating PIK3CA mutation was identified. Our results revealed no prognostic or predictive value of PIK3CA mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating PIK3CA mutation was identified in 55% of LAIBC patients with PIK3CA-mutated tumours, while no circulating mutation was found among patients with PI3KCA wild-type tumours.

Oesophageal adenocarcinoma metastasis into a microcystic meningioma: a rare occurrence of tumour to tumour metastasis

A 78 year old male was admitted with a history of a fall following seizures. This occurred 2 years post curative treatment (minimally invasive oesophagectomy with neo adjuvant chemotherapy) for an oesophageal adenocarcinoma staged T3N0M0. On examination, patient had left-sided hemiparesis. A Computed Tomography (CT) and Magnetic Resonance Image (MRI) of the head confirmed a right frontotemporal meningioma with features suggestive of internal haemorrhage or calcification and mild local mass effect. A joint decision was made between the local neuro-surgical and neurology departments to manage this conservatively. However, due to progressive neurological deterioration and a concomitant increase in the size of the haemorrhagic lesion, emergent surgical intervention was indicated. The patient underwent a Simpson one complete resection (complete tumour resection including associated dura matter and abnormal underlying bone). Postoperative histology confirmed a rare case of metastatic oesophageal adenocarcinoma to a microcystic meningioma (World Health Organization Grade I). The meningioma was the only known site of distant metastasis for the oesophageal adenocarcinoma. Our case highlights the only documented case of the adenocarcinoma subtype of oesophageal tumour metastasizing to a meningioma. This case demonstrates the rare but well documented occurrence of tumour to tumour metastasis. It highlights the importance played by imaging and clinical correlation when assessing progressively growing meningiomas in patients with a history of or underlying malignancy.

Neo-Adjuvant Chemotherapy Reduces, and Surgery Increases Immunosuppression in First-Line Treatment for Ovarian Cancer

In monotherapy, immunotherapy has a poor success rate in ovarian cancer. Upgrading to a successful combinatorial immunotherapy treatment implies knowledge of the immune changes that are induced by chemotherapy and surgery. Methodology: Patients with a new d ovarian cancer diagnosis underwent longitudinal blood samples at different time points during primary treatment. Results.: Ninety patients were included in the study (33% primary debulking surgery (PDS) with adjuvant chemotherapy (ACT), 61% neo-adjuvant chemotherapy (NACT) with interval debulking surgery (IDS), and 6% debulking surgery only). Reductions in immunosuppression were observed after NACT, but surgery reverted this effect. The immune-related proteins showed a pronounced decrease in immune stimulation and immunosuppression when primary treatment was completed. NACT with IDS leads to a transient amelioration of the immune microenvironment compared to PDS with ACT. Conclusion: The implementation of immunotherapy in the primary treatment schedule of ovarian cancer cannot be induced blindly. Carboplatin–paclitaxel seems to ameliorate the hostile immune microenvironment in ovarian cancer, which is less pronounced at the end of primary treatment. This prospective study during primary therapy for ovarian cancer that also looks at the evolution of immune-related proteins provides us with an insight into the temporary windows of opportunity in which to introduce immunotherapy during primary treatment.

The value of prognostic ultrasound features of breast cancer in different molecular subtypes with a focus on triple negative disease

The ultrasound (US) features of breast cancer have recently been shown to have prognostic significance. We aim to assess these features according to molecular subtype. 1140 consecutive US visible invasive breast cancers had US size and mean stiffness by shearwave elastography (SWE) recorded prospectively. Skin thickening (> 2.5 mm) overlying the cancer on US and the presence of posterior echo enhancement were assessed retrospectively while blinded to outcomes. Cancers were classified as luminal, triple negative (TN) or HER2 + ve based on immunohistochemistry and florescent in-situ hybridization. The relationship between US parameters and breast cancer specific survival (BCSS) was ascertained using Kaplan–Meier survival curves and ROC analysis. At median follow-up 6.3 year, there were 117 breast cancer (10%) and 132 non-breast deaths (12%). US size was significantly associated with BCSS all groups (area under the curve (AUC) 0.74 in luminal cancers, 0.64 for TN and 0.65 for HER2 + ve cancers). US skin thickening was associated most strongly with poor prognosis in TN cancers (53% vs. 80% 6 year survival, p = 0.0004). Posterior echo enhancement was associated with a poor BCSS in TN cancers (63% vs. 82% 6 year survival, p = 0.02). Mean stiffness at SWE was prognostic in the luminal and HER2 positive groups (AUC 0.69 and 0.63, respectively). In the subgroup of patients with TN cancers receiving neo-adjuvant chemotherapy posterior enhancement and skin thickening were not associated with response. US skin thickening is a poor prognostic indicator is all 3 subtypes studied, while posterior enhancement was associated with poor outcome in TN cancers