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Background Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy – a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection. Methods We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing. Results Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression. Conclusion This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.

PURPOSE Luminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate ( P = .05). CONCLUSION The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

(1) Background: Oxaliplatin is among the most neurotoxic anticancer drugs. Little data are available on the long-term prevalence and consequences of chemotherapy-induced peripheral neuropathy (CIPN), even though the third largest population of cancer survivors is made up of survivors of colorectal cancer. (2) Methods: A multicenter, cross-sectional study was conducted in 16 French centers to assess the prevalence of CIPN, as well as its consequences (neuropathic pain, anxiety, depression, and quality of life) in cancer survivors during the 5 years after the end of adjuvant oxaliplatin chemotherapy. (3) Results: Out of 406 patients, the prevalence of CIPN was 31.3% (95% confidence interval: 26.8&ndash, 36.0). Little improvement in CIPN was found over the 5 years, and 36.5% of patients with CIPN also had neuropathic pain. CIPN was associated with anxiety, depression, and deterioration of quality of life. None of the patients with CIPN were treated with duloxetine (recommendation from American Society of Clinical Oncology), and only 3.2%, 1.6%, and 1.6% were treated with pregabalin, gabapentin, and amitriptyline, respectively. (4) Conclusions: Five years after the end of chemotherapy, a quarter of patients suffered from CIPN. The present study showed marked psychological distress and uncovered a failure in management in these patients.

Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.

Background: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. Methods: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. Results: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. Conclusion: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the "in vivo" efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).

In clinical practice and the literature, malignant melanoma usually appears in typical sites where melanocytes can be found: skin, eyes meninges and anal region. Malignant melanomas of the esophagus-gastrointestinal (EGI) tract are usually metastatic. Primary and diffuse EGI tract melanoma is rare and only a few descriptions of this presentation have been found in the literature. The prognosis of EGI tract melanoma is frightening because of late diagnosis and high malignancy potential. Treatment is based essentially on surgery. The objective of the present study is to specify the clinical and therapeutic aspects of primary digestive melanoma.

Background BC screening by mammography is associated with a significant reduction in mortality (19 % overall reduction of the relative risk), however with significant limitations and debatable cost-effectiveness. Screening individuals for cancer using liquid biopsies (LB) represents an unmet need. We report the first prospective “proof of concept” study using the QO technology combined with an AI approach using the concept of “MPnV” applied to BC detection. Methods QO (femto/atto-second infrared laser spectroscopy) on LB is a simple, non-invasive and reproducible method allowing to identify individualized molecular spectra (MS). These highly detailed MS can be correlated to physiological or pathological changes allowing detection and translation of differences. Integrated into a super-computational approach using a non-hierarchical deep data mining strategy (MPnV concept), MS could discriminate individuals with and without BC. The plasma of 68 controls and 27 BC patients, accrued at the King Saud University BC screening program, Riyadh, Saudi Arabia (KSA), were studied by QO (Max Planck Institute of Quantum Optics /Ludwig Maximillian University Munich, Garching, Germany). The MS were analysed on the Shaheen II supercomputer at King Abdallah University for Science and Technology (KAUST), KSA, in order to generate comparative algorithms. Results The use of special feature selection, followed by class analysis allowed to differentiate profiles between the two groups with a sensitivity of 97% and a specificity of 72% (variables n = 1,100). A more in-depth analysis led to 99% sensitivity, but with a lower specificity of 64%. Further analysis of the series, using an age-matched approach led to 97% sensitivity with 98% specificity in differentiating women with or without BC. Conclusions These results warrant a large scale prospective validation BC screening trial (ongoing) and “proof of concept trials” in other frequent cancers, in particular those without existing screening programs. Editorial acknowledgement Prof. Ferenc Krausz, Director, and Dr. Mihaela Zigman, Leader of the Broadband Infrared Diagnostics, Max Planck Institute of Quantum Optics (MPQ), Faculty of Physics at Ludwig-Maximilians Universitat Munchen (LMU), Garching, Germany. Legal entity responsible for the study Jean Marc Nabholtz, Oncology Centre, King Saud University, Riyadh, Saudi Arabia. Funding 1. Oncology Centre, King Saud University Medical City, King Saud University, Saudi Arabia. 2. Max-Planck-Institut fur Quantenoptik and Faculty of Physics at Ludwig-Maximilians Universitat Munchen, Garching, Germany. 3. Computational Bioscience Research Centre, King Abdallah University for Science and Technology (KAUST), Thuwal, Saudi Arabia. Disclosure M.R.K. Bahadoor: Travel / Accommodation / Expenses, ASCO Participation Funded: Pfizer; Advisory / Consultancy, Pancreas Expert Opinion Advisory: Baxter. All other authors have declared no conflicts of interest.

Background NA chemotherapy (CT) +/- anti-Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in HR+/Her2- BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs. Methods This is a multicenter phase III, 3rd generation NA trial performed in 34 centers and 7 countries of Middle-East and North Africa (MENA Region). The objective is to investigate the potential role of adding Palbociclib to ET (Fulvestrant +/- Goserelin) compared to ET alone as NA therapy of HR+/Her2- operable BC sensitive to ET. The primary endpoint is pCR with the hypothesis that the addition of Palbociclib would increase the pCR rate from 5% to 15%. Clinical/radiological response, conservative surgery rate, safety, disease-free and OS are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies. Results A total of 400 pre and post-menopausal pts with stage II and IIIA are planned to be recruited. Oncotype DX is performed upfront in order to eliminate CT candidates. All pts with a recurrence score (RS) Conclusions SAFIA trial aims to evaluate whether or not the addition of a CDK 4/6 inhibitor to pts sensitive to ET would validate a neo-adjuvant strategy without CT in luminal operable BC. Clinical trial identification NCT03447132. Legal entity responsible for the study International Cancer Research Group (ICRG). Funding Pfizer, AstraZeneca and Genomic Health. Disclosure All authors have declared no conflicts of interest.

e12592 Background: Breast cancer is the second most common cancer and the fifth most common cause of cancer mortality worldwide. The functional relationship between inflammation and cancer is an old concept of cancero- genesis, and it is now clear that inflammatory process certainly potentiates and/or promotes neoplastic risk. However, many of the molecular and cellular mechanisms mediating this relationship remain unresolved. The aim of this study is to measure the level of circulating cytokines (IL17, IL6, IL22, IL23 and TNFα) in breast cancer patients in Tunisia, and to evaluate their implication as prognostic factors. Methods: Serum samples were collected prospectively from sixty breast cancer patients in Tunisia. TNF-α and IL6 levels were determined using the technique of a solid-phase, two-site chemo-luminescent enzyme immune-metric assay (Immulite 1000, USA). Serum levels of IL17, IL22 and IL23 were measured by enzyme-linked immunosorbent assays (ELISA) sandwich method. Results: The mean age of patients is 48 years, and fourth of them were metastatic. The mean level of cytokines IL6, IL17, TNFα, IL22 and IL23 were respectively 4.80 ± 7.26 pg/ ml (min 2, max 36.80 pg/ ml), 0.27 ± 0.69 pg/ ml (min 0, max 3.62 pg/ ml), 5.93 ± 2.27 pg/ ml (min 4, max 15.30 pg/ml), 50.82 ± 34.78 p/ml (min 26.48, max 199.48 pg/ ml) and 18.05 ± 30.91 pg/ ml (min 0, max 200.21 pg/ml). Serum IL6 level was significantly higher in advanced stages (p = 0.013), especially in metastatic cases (p = 0.001) and in patients who had recurrent disease (p = 0.010). High level of TNFα was also significantly associated with advanced stage (stage III and IV) (p = 0.019), and high level of IL22 was significantly associated with a high histopathological grade (Grade III of Bloom-Richardson grade (SBR)) (p = 0.028). IL23 was found to be significantly increased in lymph node metastatic cases (p = 0.042) and in young patients < 35 years (p = 0.034). Finally, the level of IL17 was significantly higher in patients who had recurrent disease (p = 0.018). Conclusions: Our results highlight the role of certain circulating cytokines as potential prognostic biomarkers in breast cancer patients. The serum analysis of these cytokines, which could contribute to tumor growth and progression, may help to identify groups of patients with poor prognosis and who may need more aggressive treatment. This correlation needs to be evaluated in large prospective validating trials and suggests a rational for the development and use of cytokine blockade in treatment of some groups of breast cancer patients.

e15130 Background: Colorectal cancer is the third most common malignancy and fourth most common cause of cancer mortality worldwide. It is responsible for more than 600,000 deaths annually, and incidence rates are increasing in most of the developing countries. Pathophysiology implicates pro-inflammatory conditions that promote the tumor malignant progression, invasion, and metastasis. The aim of this study is to measure the level of circulating cytokines (IL1b, IL6, IL8, IL10, IL22, IL23 and TNFα) in sixty colorectal cancer patients in Tunisia and to evaluate their implication as prognostic factors. Methods: Serum samples were collected prospectively from a cohort of sixty colorectal cancer patients in Tunisia. Levels of circulating inflammatory cytokines, TNF-α, IL1b, IL6 and IL8 were measured using the technique of a solid-phase, two-site chemo-luminescent enzyme immune-metric assay (Immulite 1000, Simens, USA). Serum levels of IL10 were measured by enzyme-linked immunosorbent assays (ELISA) sandwich method. Results: The mean age of patients is 58 years (24–82 years), Thirty-sex among them were m and 24 women with sex ratio of 1.5. Twenty-five patients were at metastatic setting, and hepatic metastasis was found in 25% of cases. The mean level of cytokines Il6, IL10, TNFα, IL8 and IL1b were respectively 12.26 +/- 18.7 pg/ ml (min 2, max 117pg/ ml), 0.93 +/- 5.23 pg/ ml (min 0, max 39.35 pg/ml), 8.31 +/- 4.99 pg/ ml (min 4, max 27.20 pg/ ml), 61.9 +/- 159.71 pg/ml (min 5, max 1173 pg/ ml) and 1.13 +/- 3.34 pg/ ml (min 5, max 15.7pg/ml. We found a significant correlation between a high level of IL8 and metastatic disease (p=0.001), especially in mutant RAS cases (p=0.001). We found also a significant correlation between high level of IL1b and lymphovascular invasion (p=0.013) and young patients (p=0.01). On the other hand, there was significant correlation between IL8 and IL6 (r = 0.560, p = 0.00001); IL8 and TNFα (r = 0.404, p = 0.001); and IL10 with IL1b (r = 0.297, p = 0.021). Conclusions: Our results highlight the role of circulating IL8, TNFα, IL1b and IL10 as potential prognostic biomarkers in colorectal cancer patients. These cytokines could contribute to tumor growth and progression, namely for IL-8 level that was significantly correlated with poor prognosis and advanced stages. This correlation needs to be evaluated in large prospective trials and suggests a rational for the development and use of cytokine blockade in treatment of colorectal cancer patients.

In clinical practice and the literature, malignant melanoma usually appears in typical sites where melanocytes can be found: skin, eyes meninges and anal region. Malignant melanomas of the esophagus-gastrointestinal (EGI) tract are usually metastatic. Primary and diffuse EGI tract melanoma is rare and only a few descriptions of this presentation have been found in the literature. The prognosis of EGI tract melanoma is frightening because of late diagnosis and high malignancy potential. Treatment is based essentially on surgery. The objective of the present study is to specify the clinical and therapeutic aspects of primary digestive melanoma.

Background Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the epithelial growth factor receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline–taxane-based chemotherapy in patients with operable, stage II–III, TNBC. Patients and methods Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for eight cycles q.3 weeks combined with four cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m2) q.3 weeks, followed by four cycles of docetaxel (T: 100 mg/m2) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathologic complete response (pCR) in assessable patients was the main end point while clinical response, toxicity and ancillary studies were secondary end points. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody. Results Sixty patients were included with 47 assessable for pathologic response. The pCR rates were 46.8% [95% confidence interval (CI): 32.5% to 61.1%] and 55.3% [95% CI: 41.1% to 69.5%] according, respectively, to Chevallier and Sataloff classifications. The complete clinical response (cCR) rate was 37.5%. Conservative surgery was carried out in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR. Conclusions Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with a high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC. Clinical Trial Number NCT00933517.