Downstaging Of Cancer Research Articles

Screening and prevention of ovarian cancer.

Ovarian cancer remains the most lethal gynaecological malignancy with 314 000 cases and 207 000 deaths annually worldwide. Ovarian cancer cases and deaths are predicted to increase in Australia by 42% and 55% respectively by 2040. Earlier detection and significant downstaging of ovarian cancer have been demonstrated with multimodal screening in the largest randomised controlled trial of ovarian cancer screening in women at average population risk. However, none of the randomised trials have demonstrated a mortality benefit. Therefore, ovarian cancer screening is not currently recommended in women at average population risk. More frequent surveillance for ovarian cancer every three to four months in women at high risk has shown good performance characteristics and significant downstaging, but there is no available information on a survival benefit. Population testing offers an emerging novel strategy to identify women at high risk who can benefit from ovarian cancer prevention. Novel multicancer early detection biomarker, longitudinal multiple marker strategies, and new biomarkers are being investigated and evaluated for ovarian cancer screening. Risk-reducing salpingo-oophorectomy (RRSO) decreases ovarian cancer incidence and mortality and is recommended for women at over a 4-5% lifetime risk of ovarian cancer. Pre-menopausal women without contraindications to hormone replacement therapy (HRT) undergoing RRSO should be offered HRT until 51 years of age to minimise the detrimental consequences of premature menopause. Currently risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) should only be offered to women at increased risk of ovarian cancer within the context of a research trial. Pre-menopausal early salpingectomy is associated with fewer menopausal symptoms and better sexual function than bilateral salpingo-oophorectomy. A Sectioning and Extensively Examining the Fimbria (SEE-FIM) protocol should be used for histopathological assessment in women at high risk of ovarian cancer who are undergoing surgical prevention. Opportunistic salpingectomy may be offered at routine gynaecological surgery to all women who have completed their family. Long term prospective opportunistic salpingectomy studies are needed to determine the effect size of ovarian cancer risk reduction and the impact on menopause.

The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

Outcomes of a Multidisciplinary Team in the Management of Patients with Early-Stage Breast Cancer Undergoing Neoadjuvant Chemotherapy at a Community Cancer Center.

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2-. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.

Preoperative downstaging of pancreatic cancer is associated with improved survival after multi-agent chemotherapy, but not after radiation

BackgroundDownstaging has been associated with improved survival for many cancers. However, the implications of downstaging are unclear for pancreatic cancer in an era of effective neoadjuvant systemic chemotherapy. MethodsNCDB retrospective cohort study of resected pancreatic carcinoma treated with neoadjuvant therapy. ResultsThe study included 73,985 patients: 66,589 with no neoadjuvant therapy, 2,102 neoadjuvant radiation therapy (N-RT), 3,195 neoadjuvant multiagent chemotherapy (N-MAC) and 2.099 with both neoadjuvant radiation and multiagent chemotherapy. There was increased use of N-MAC over the period of this study. Patients selected for treatment with N-MAC had longer survival from surgery on univariate (23.1 vs. 18.7 months, p = < 0.01) and multivariate analyses HR 0.81 (0.76–0.87, p < 0.001) compared to those selected with N-RT. Downstaging was similar in N-RT and N-MAC groups (25.1 vs. 24.1%, p = 0.43). Downstaging following N-MAC was associated with a survival benefit, HR 0.85 (0.74–0.98). However, downstaging following N-RT was not associated with a survival advantage, HR 1.12 (0.99–0.99). ConclusionClinicians have rapidly adopted N-MAC for treatment of pancreatic cancer. Although the rates of downstaging are similar between treatment groups, response translates into increased survival only with N-MAC and not with N-RT.

Modern Active Surveillance in Prostate Cancer: A Narrative Review

The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection criteria and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection criteria recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection.

Downstaging of Rectal Cancer Following Neoadjuvant Chemoradiotherapy; How Far Could Functional MRI Support Organ Preservation Approach

Downstaging of Rectal Cancer Following Neoadjuvant Chemoradiotherapy; How Far Could Functional MRI Support Organ Preservation Approach

Endoscopic Submucosal Dissection for Esophageal Squamous Cell High-grade Dysplasia in a Patient with Plummer Vinson Syndrome

AbstractA 35-year female with Plummer Vinson syndrome (PVS) presented with a history of progressive dysphagia over six months, not responding to iron therapy and endoscopic dilatations. Her upper gastrointestinal endoscopy showed a post-cricoid web dilated using a Savary-Gilliard dilator. On NBI, a long segment circumferential lesion with abnormal microvascular architecture was noted in the mid esophagus. Biopsy showed high-grade dysplastic squamous epithelium. The patient underwent minimally invasive, circumferential endoscopic submucosal dissection (ESD) and received oral prednisolone to prevent stricture formation. Resected margins were free of dysplasia. At follow-up there was no evidence of recurrence or stricture formation. To our knowledge, this is the first case of PVS with squamous proliferation with high-grade dysplasia that was successfully treated with circumferential ESD. Screening endoscopy helps in the downstaging of early cancer, and timely intervention helps to treat this with a minimally invasive approach like ESD.

Real-world outcomes of neoadjuvant chemotherapy for breast cancer: Reflections from a community cancer center.

e18690 Background: Neoadjuvant chemotherapy (NAC) has been historically reserved for patients with locally advanced breast cancers. The utilization of NAC remains highly variable in clinical practice based on tumor size and receptor status. The decision to pursue NAC is often based on discussions by a multidisciplinary team (MDT). This study aims to look at real-world data describing the contemporary use of NAC in patients with early-stage operable breast cancer in a community cancer center and evaluate the effectiveness of MDT at our institution. Methods: We conducted a retrospective descriptive study at UMass Chan-Baystate between Oct 2018 and Oct 2020. We included patients receiving NAC for early-stage operable or locally advanced breast cancer. We excluded patients receiving neoadjuvant endocrine therapy. Primary outcomes were rates of pathological complete response (pCR) after surgery. Secondary outcomes were referral timeliness back to the breast surgeon and radiation oncologist, downstaging of cancer in the breast and axilla. Results: Ninety-three patients underwent NAC, of which 84% were white. The mean age was 56.6 yrs. Of these, 86 (93%) had clinical stage II or III cancer, and 80 (86%) had positive lymph nodes. Forty-two patients (46%) were ER positive, 28 (30%) were HER2 positive and 39 (43%) were triple negative. The most common indication for NAC was to downstage axilla (42%) and for HER2 tailoring of treatment (26%). Of the 93 patients, 23 (25%) achieved pCR; 12 (52%) had triple-negative, 7 (30%) had ER-HER2+, 3 (13%) had ER+HER2+ and 1 (4%) had ER+HER2- breast cancer. Eighty-four patients (91%) had downstaging of breast tumor, and 30 (32.3%) had axillary downstaging. Seventy-eight patients (84%) received adjuvant radiation (RT). All patients (N = 93, 100%) followed up with a surgeon prior to completion of NAC, although only 48 (50%) returned to radiation oncology. The mean time from surgery to RT was 64 days, and 6% underwent RT for more than two weeks beyond the expected time. Conclusions: Overall pCR rates were low; however, a third of patients had axillary downstaging, and the majority had breast tumor downstaging. Of the patients in our cohort who achieved pCR, the majority were triple-negative, followed by HER2 positive, consistent with overall trends. All patients were re-referred to the surgeon prior to completion of NAC for surgical planning and the average time from surgery to radiation was within national standards highlighting effective MDT involvement in the care of patients at our institution.[Table: see text]

Safety and Efficacy of Multiple Sirt Treatments with Resin Microspheres® Y-90, Combined with Surgery as Bridge/Downstage to Hepatic Transplant: A Case Report and Literature Review

Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Hepatocellular carcinoma (HCC) represents about 90% of primary liver cancers and constitutes a major global health problem. Combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) represents about 10% of total HCC, and it is by definition a highly heterogeneous tumor, which confers a negative impact on tumor prognosis compared to HCC. Selective Internal Radiation Therapy (SIRT) using yttrium-90 microspheres shows a good safety profile and local tumor control, and it is now considered among the therapeutic options for liver cancer downstaging before liver transplant (LT). We present the case of a young man with a diagnosis of hepatitis B cirrhosis and subsequent finding of advanced primary neoplasm with particularly aggressive histology of cHCC‐CCA. The patient underwent two SIRT treatments in 6 months. The first SIRT treatment provided an adequate downstaging to surgery, then a successful SIRT retreatment after surgery, in a bridging purpose, allowed for liver transplantation, with complete necrosis at explant. We demonstrated the feasibility and safety of multi treatment approaches, with two successive SIRT treatments and surgery. We outline the efficacy of an aggressive downstaging strategy allowing a potentially curative therapy as liver transplant.

Treatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials

Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab+ olaparib arm (n= 72) and corresponding controls (n= 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n= 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

Surgeon-Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients' Short-Term Outcome.

Simple SummaryAppropriate lymph node harvesting for patients with gastric cancer is fundamental for a correct staging and is strongly related to survival. In this study, we present a new protocol for on-site macroscopic evaluation and sampling of lymph nodes for gastric cancer patients. With the joint collaboration of surgeons and pathologists, our method aims to provide the largest possible number of analyzed lymph nodes per patient, allowing for a better staging. We are convinced that this approach is routinely feasible, and our preliminary results seem to confirm better patient stratification compared to other lymph node dissection methods.The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a critical factor affecting the outcome of patients. None of the techniques proposed so far have demonstrated a real efficiency in increasing the number of identified lymph nodes. To harvest the maximum number of lymph nodes, we designed a protocol for on-site macroscopic evaluation and sampling of lymph nodes according to the Japanese Gastric Cancer Association protocol. The procedure was carried out by a surgeon/pathologist team in the operating room. We enrolled one hundred patients, 50 of whom belonged to the study group and 50 to a control group. The study group included patients who underwent lymph node dissection following the proposed protocol; the control group encompassed patients undergoing standard procedures for sampling. We compared the number and maximum diameter of lymph nodes collected in both groups, as well as some postoperative variables, the 30-day mortality and the overall survival. In the study group, the mean number of lymph nodes harvested was higher than the control one (p = 0.001). Moreover, by applying the proposed technique, we sampled lymph nodes with a very small diameter, some of which were metastatic. Noticeably, no difference in terms of postoperative course was identified between the two groups, again supporting the feasibility of an extended lymphadenectomy. By comparing the prognosis of patients, a better overall survival (p = 0.03) was detected in the study group; however, to date, no long-term follow-up is available. Interestingly, patients with metastasis in node stations number 8, 9, 11 or with skip metastasis, experienced a worse outcome and died. Based on our preliminary results, the pathologist/surgeon team approach seems to be a reliable option, despite of a slight increase in sfaff workload and technical cost. It allows for the harvesting of a larger number of lymph nodes and improves the outcome of the patients thanks to more precise staging and therapy. Nevertheless, since a higher number of patients are necessary to confirm our findings and assess the impact of this technique on oncological outcome, our study could serve as a proof-of-concept for a larger, multicentric collaboration.

Breast cancer awareness and downstaging practices among adult women in Gulu City Main Market in Northern Uganda: A cross-sectional study

Background: Breast Cancer is one of the most common cancers that occur universally among women. The disability-adjusted life years lost by women to breast cancer globally are more than any other cancer. Breast cancer occurs in women worldwide after puberty with increasing rates in later life. Improvements in breast cancer survival began in the 1980s in countries where early detection programs combined with different modes of treatment to eradicate the invasive form of the disease are practiced. Recent data show a higher prevalence of breast cancer among women in Northern Uganda compared to the rest of the country. This study aimed to determine factors associated with breast cancer awareness, breast self-examination, clinical breast examination, and other modalities for screening and early breast cancer detection among adult women in Gulu Main Market. Methods: We conducted a cross-sectional study in Gulu's Main Market in 2020. We recruited Ninety-eight adult women for the study using a random sampling method. The questionnaire had an internal validity of Cronbach's α=0.72, and a local IRB approved the study. We used SPSS version 26.0 for data analysis, and a p-value less than 0.05 was considered significant. Results: Most participants were 20-29 years 41(41.8%), married 44(44.9%), monthly incomes of more than one million shillings 51(52.2%), Acholi 81(82.7%), Catholics 46(46.9%), vendors 75(76.5%), work duration in the Market (1-10 years) 64(65.4%), primary level of education 39(39.8%), and had 1-2 pregnancies 37(37.8%). The independent factors associated with breast cancer awareness, breast self-examination, and clinical breast examination were vendor (primary occupation) (β=-0.130, t=-2.979, p=0.004), work duration in the Main Market (1-10 years) (β=-0.186, t=-2.452, p=0.016), and the highest level of education (β=-0.091, t=-2.506, p=0.014). Conclusions: Breast cancer awareness and downstaging practices among adult women in Gulu's Main Market are thought-provoking. Women with better socioeconomic status (higher education level, moderate work duration in the Market, and vendors) in Gulu Main Market were more likely aware and practiced breast cancer downstaging activities. There is a need to strengthen publicity on breast cancer-related knowledge for lower-income occupational groups and those with lower educational levels to understand better the importance of conducting early breast cancer detection activities.

National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis.

In some countries, breast cancer age-standardised mortality rates have decreased by 2-4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions. In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less. 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (β=-0·12, 95% CI -0·16 to -0·08) and increasing numbers of public cancer centres (β=-0·23, -0·36 to -0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening. Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. None.

Neoadjuvant therapy contributes to nodal downstaging of pancreatic cancer.

This study aimed to assess the impact of neoadjuvant therapy (NAT) for borderline resectable or locally advanced pancreatic cancer (BR/LAPC) on the American Joint Commission on Cancer (AJCC) nodal status. The medical records of BR/LAPC patients who underwent surgery with curative intent were retrospectively reviewed. The nodal status was compared between patients who underwent upfront surgery (UFS) and those who received NAT. Moreover, clinicopathological factors and prognostic factors for overall survival were analyzed. In all, 200 patients with BR/LAPC, 78 with UFS, and 122 with NAT were enrolled. The nodal status was significantly lower in patients after NAT than after UFS (p = 0.011). A multivariate analysis of overall survival showed that UFS (hazard ratio (HR) 1.61, p = 0.024) and N2 status (HR 2.69, p < 0.001) were independent poor prognostic factors. The median serum carbohydrate antigen (CA) 19-9 level after NAT in N2 patients was 105 U/mL, which was significantly higher than that of patients with N0 (p = 0.004) and N1 (p = 0.008) status. Patients with BR/LAPC who underwent surgery after NAT had significantly lower N2 status and better prognosis than patients who underwent UFS. Elevated CA19-9 levels after NAT indicated a higher nodal status.

Osimertinib as neoadjuvant treatment for resectable stage II-IIIB EGFR mutant lung adenocarcinoma (NEOS).

8524 Background: Neoadjuvant treatment has demonstrated efficacy in several types of cancer and is increasingly used for the treatment of early-stage cancers with the potential of cancer downstaging to enhance complete surgical resection and to improve clinical outcomes. Recent evidences have demonstrated that the neoadjuvant use of first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may provide clinically meaningful improvement in EGFRm non-small cell lung cancer (NSCLC) patients, however, limited data were reported on osimertinib, the third-generation EGFR-TKI, in the neoadjuvant setting. Here we present an interim analysis of osimertinib as neoadjuvant treatment for resectable EGFRm NSCLC. Methods: NEOS is a prospective, multi-center, single-arm study to evaluate the efficacy and safety of osimertinib as neoadjuvant treatment in resectable EGFRm (19del/L858R) lung adenocarcinoma. Eligible patients were treated with osimertinib 80 mg orally per day for six weeks followed by surgery. Assessment of response to neoadjuvant therapy was performed according to RECIST 1.1. The primary endpoint was response rate. Secondary endpoints included safety, R0 surgical resection rate, quality of life, major pathologic response (MPR) rate, pathological complete response (pCR) rate, and N2 downstaging rate. Results: As of Dec. 17, 2020, 18 eligible patients (median age 61 [range 46-73], 27.8% male, 22.2% ECOG PS 1) have been enrolled. Patients with clinical stages IIa, IIb, and IIIa (8th AJCC) accounted for 16.7%, 22.2% and 61.1%, respectively. Half (9/18) of the patients had EGFR exon 21 L858R mutations and the other half (9/18) had EGFR exon 19del mutations. Amongst all 15 patients who completed efficacy assessment after neoadjuvant osimertinib, the response rate (RR) was 73.3% (11/15) and the disease control rate (DCR) was 100% (15/15). R0 surgical resection was performed in 93.3% (14/15) patients. Pathological downstaging occurred in 53.3% (8/15) patients. 42.9% (3/7) of the patients with confirmed N2 lymph nodes experienced downstaging to N0 disease after receiving neoadjuvant osimertinib. One patient was identified with a pCR. Adverse events (AEs) were reported in 66.7% (12/18) of patients, with the most common AE being rash (8/18, 44.4%), oral ulceration (8/18, 44.4%), and diarrhea (5/18, 27.8%). No grade 3-5 AEs or serious AEs were reported. Conclusions: Interim analysis from this study indicated neoadjuvant osimertinib as an effective and feasible treatment in patients with resectable stage II-IIIB EGFRm NSCLC. The trial is ongoing and the final results will be provided in the future. Clinical trial information: ChiCTR1800016948.

Downstaging of cervical cancer in Tanzania over a 16-year period.

Globally, the highest cervical cancer mortality rates are found in East Africa. Visual inspection with acetic acid (VIA)-based screening in resource-poor settings has been shown to decrease the proportion of women presenting with late-stage cervical cancer, a process known as clinical downstaging. The only cancer treatment center in Tanzania, Ocean Road Cancer Institute (ORCI) in Dar es Salaam, opened a VIA-based cervical cancer screening program in 2002. We reviewed 6,676 medical records of cervical cancer patients at the ORCI from 2002-2011 to 2014-2018 for stage at diagnosis and screening status, among other variables. We investigated whether clinical downstaging occurred in this period among women screened at the ORCI, when compared to unscreened women. Our results indicated that the proportion of women presenting with late-stage cervical cancer among women screened at the ORCI decreased by 27.7% over the 16-year period (χ2 = 16.99; p = 0.0002). Among unscreened women, a non-significant 13.2% decrease in late-stage disease was observed (χ2 = 1.74; p = 0.4179). Our results suggest clinical downstaging occurred among women screened at the ORCI over the 16-year period, and this difference may be attributed to the screening program as the same decrease in stage was not observed among unscreened women during the same time period. At present, less than one percent of Tanzanian women receive yearly cervical cancer screenings. Access to screening through expansion of the ORCI screening clinic and the creation of more clinics should be prioritized.

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Ovarian Surface Epithelial Neoplasms and its Association with Histological Type, Grade, Clinical Stage and Tumour Metastasis

Introduction: Ovarian carcinoma is one of the most common gynaecologic cancers and remains the leading cause of death as the patients are diagnosed at the advanced stage of the disease. Vascular Endothelial Growth Factor (VEGF), a promoter of angiogenesis, participates in multiple mechanisms to promote ovarian cancer cell growth, angiopoiesis and distant metastasis. So, it is a promising target for antiangiogenic therapy in management and downstaging of ovarian cancer. Aim: To evaluate the immunohistochemical expression of VEGF in different surface epithelial neoplasms of ovary and compare it with histological type, grade and stage in malignant cases. Materials and Methods: This was an observational cross-sectional study conducted from August 2018 to January 2020. Total 50 consecutive cases of surface epithelial ovarian neoplasms received in Pathology Department of Srirama Chandra Bhanja (SCB) Medical College, Cuttack were examined for expression of VEGF by Immunohistochemistry (IHC). Data was examined to find association of VEGF expression with demographic profile, grade, stage and were analysed statistically using Statistical Package for the Social Sciences (SPSS) software version 21.0. Statistical significance was tested by using Pearson’s chi-square test. The p&lt;0.05 was considered significant. Results: Total 50 cases of ovarian surface epithelial neoplasms of different types and grade were included in the study. A 42 of the 50 cases (84%) showed VEGF expression. Out of the 42 positive cases, 18 were high VEGF expressors and 24 were low VEGF expressors. The VEGF expression was significantly higher in carcinomas as compared to benign and borderline neoplasms and also in high grade malignancies in comparison to low grade (p≤0.001). Conclusion: The study shows that the differential expression of VEGF in different ovarian epithelial neoplasms which can be a diagnostic and prognostic tool and can be applied as a VEGF targeted therapy in certain group of patients.

Co-administration of H-ferritin-doxorubicin and Trastuzumab in neoadjuvant setting improves efficacy and prevents cardiotoxicity in HER2\u2009+\u2009murine breast cancer model

Neoadjuvant chemotherapy has been established as the standard of care for HER2-positive breast cancer since it allows cancer down-staging, up to pathological complete response. The standard of care in the neoadjuvant setting for HER2-positive breast cancer is a combination of highly cytotoxic drugs such as anthracyclines and the anti-HER2 monoclonal antibody. Despite this cocktail allows a pathological complete response in up to 50%, their co-administration is strongly limited by intrinsic cardiotoxicity. Therefore, only a sequential administration of anthracyclines and the anti-HER2 treatment is allowed. Here, we propose the anthracycline formulation in H-Ferritin nanocages as promising candidate to solve this unmet clinical need, thanks to its capability to increase anthracyclines efficacy while reducing their cardiotoxicity. Treating a murine model of HER2-positive breast cancer with co-administration of Trastuzumab and H-Ferritin anthracycline nanoformulation, we demonstrate an improved tumor penetration of drugs, leading to increased anticancer efficacy and reduced of cardiotoxicity.

Predicting Response to Neoadjuvant Therapy in Colorectal Cancer Patients the Role of Messenger-and Micro-RNA Profiling.

Colorectal cancer patients’ responses to neoadjuvant therapy undergo broad inter-individual variations. The aim of this systematic review is to identify a molecular signature that is predictive of colon cancer downstaging and/or downgrading after neoadjuvant therapy. Among the hundreds analysed in the available studies, only 19 messenger-RNAs (mRNAs) and six micro-RNAs (miRNAs) were differentially expressed in responders versus non-responders in two or more independent studies. Therefore, a mRNA/miRNA signature can be designed accordingly, with limitations caused by the retrospective nature of these studies, the heterogeneity in study designs and the downgrading/downstaging assessment criteria. This signature can be proposed to tailor neoadjuvant therapy regimens on an individual basis.

Diagnostic accuracy of CT-staging of advanced gastric cancer following neoadjuvant chemotherapy.

4551 Background: Neoadjuvant or perioperative chemotherapy has been accepted as a standard treatment globally in patients (pts) with locally advanced gastric cancer (LAGC). In PRODIGY phase III study (n = 530), we have demonstrated that neoadjuvant chemotherapy with DOS regimen (docetaxel, oxaliplatin, S-1) led to significant tumor downstaging and improved PFS in Korean LAGC pts (Kang, et al. ESMO 2019). Although CT has been performed to re-stage the tumor after neoadjuvant chemotherapy, there has been a relative paucity of diagnostic accuracy data. This study is to evaluate the diagnostic performance of restaging of LAGC after neoadjuvant chemotherapy using CT in PRODIGY study population. Methods: Of 266 pts, who had been diagnosed LAGC of T2-4 or N+ stage as assessed with CT and randomized to neoadjuvant chemotherapy arm (CSC) in PRODIGY study, 214 pts underwent gastrectomy were included in this analysis. The post-chemotherapy T- and N- stage was determined based on CT scan taken just prior to surgery and compared with the pathologic stage (AJCC 7th edition). Two experienced radiologists independently evaluated depth of primary tumor and reached consensus if any discrepancy between two readers. Diameter of short axis of the largest regional lymph node was measured to predict metastatic lymph node. Result of histopathologic T- and N-staging using surgical specimen was used as reference standard. Results: The study cohort consisted of pathologic T0 (n = 22), T1(n = 39), T2(n = 31), T3(n = 79), and T4(n = 43). The overall diagnostic accuracy of CT was 45%. For each T-stage, accuracy of T0,T1,T2,T3, and T4 was 0%, 26%, 29%, 55% and 79%, respectively. Rate of over- and under- staging was 47% and 8%, respectively. Accuracy for prediction of downstaging to early gastric cancer (T0-T1) was 83%. Interobserver agreement of T-staging was moderate (k = 0.41). There were 98 patients of N+ and 116 patients of N- at histopathology. Area under the curve of receiver operating characteristics to differentiate lymph node metastasis was 0.63. Sensitivity and specificity of size criteria of the largest lymph node (cut off value: &gt; 6mm, &gt; 7mm, and &gt; 8mm) to predict pathologic N+ were 90% and 17%, 78% and 34%, and 68% and 51%, respectively. Conclusions: Re-staging using CT after neoadjuvant chemotherapy showed suboptimal accuracy and over-staged residual tumor. However, it predicted downstaging of gastric cancer with high accuracy.