Primary Systemic Chemotherapy Research Articles

EXTH-77. INFANT-TYPE HEMISPHERIC GLIOMAS WITH INITIAL RESPONSE FOLLOWED BY RESISTANCE ON TARGETED AGENTS

Abstract Pediatric-type Diffuse High Grade Gliomas (pHGG) are a rare brain tumor with high mortality and need for more effective treatment options. pHGG’s make up only about 10% of CNS tumors but are responsible for a majority of the deaths. Infant-type Hemispheric Gliomas are a subtype of pHGG with tyrosine kinase alterations in genes such as ROS1, ALK, MET, and NTRK1-3. Despite advances in categorization and targeted therapies, the natural history of patients with infant HGG treated with targeted therapy over time needs to be better characterized, including the durability of objective responses. We present a retrospective case series involving two patients diagnosed with Infant-type Hemispheric Gliomas at Arkansas Children’s Hospital from 2022-2024. Each diagnosis was determined based on histology, targeted tumor sequencing, and methylation profiling. Both patients were initially treated with primary surgical resection and systemic chemotherapy. Each patient experienced disease progression. Actionable pathogenic mutations were identified in both patients (a MET alteration in patient 1 who was then started on Cabozantinib, an ALK fusion in patient 2 subsequently treated with Lorlatinib) with an objective disease response in both patients. In both cases, further relapse occurred while on targeted inhibition. Relapse specimen was not available for patient 1, but for patient 2, recurrent tumor sequencing revealed similar genetics from the diagnostic specimen except for a MET copy number gain suggesting the mechanism of resistance in this patient. Infant-type Hemispheric Gliomas with targetable alterations can show meaningful responses to pathway inhibition. Relapse after initial response may warrant additional surgical sample to identify new alterations which can lead to changes in therapy. Larger prospective cohorts are needed to study targeted agents in this population, and early integration during radiation or after initial diagnosis may be needed.

Unveiling the Uncommon: A Case of Parietal Rhabdomyosarcoma in a 60-year-old Woman

Malignant mesenchymal tumours are rare, aggressive neoplasms originating from mesenchymal tissues. These tumours are characterised by a high metastatic potential and pose significant diagnostic and therapeutic challenges. Mesenchymal tumours are of interest to oncologists because of their comparatively low occurrence, especially those with a high proliferation index. Authors report a case of a 60-year-old female who presented to the tertiary care rural hospital with persistent headaches, dizziness, and respiratory distress. Imaging studies revealed a heterogeneously enhancing soft-tissue density lesion in the right parietal region with extensive metastasis to both lungs. Histopathological analysis of the parietal lesion indicated features suspicious of a highgrade malignant tumour of muscular origin. Immunohistochemistry results were conclusive for Rhabdomyosarcoma. The patient was treated with radiation therapy for the primary tumour site and systemic chemotherapy, including doxorubicin and ifosfamide, for the metastasis. This case highlights the aggressive nature of malignant mesenchymal tumours and the complexities involved in their management. The high Ki-67 index and extensive metastasis indicate a poor prognosis. A multidisciplinary approach is crucial for symptom management and improving quality of life. Early detection, accurate diagnosis, and a comprehensive, multidisciplinary treatment strategy are essential for managing these challenging cases. Patients with such tumours typically have a bad prognosis since they have a significant chance of the tumour spreading to other organs, such as the liver, lungs, and bones. This case report aims to highlight the clinical presentation, diagnostic process, and therapeutic challenges associated with this aggressive tumour type, contributing to the limited but growing body of literature on rhabdomyosarcoma.

The right ventricle is not spared by the cardiotoxic effects of chemotherapy for breast cancer. Results of SAFE trial

Abstract Functional abnormalities of the right ventricle(RV) have been demonstrated in cancer patients receiving anthracyclines and trastuzumab. AHA/ACC 2022 guidelines for heart failure recommend angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers for asymptomatic LV dysfunction. It would be important to determine whether these neurohormonal modulators are beneficial for the RV as well. Design The SAFE trial (NCT: 2236806) is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Patients with breast cancer were recruited between July 2015 and June 2020, and considered eligible if they had indicated primary or postoperative systemic chemotherapy with an anthracycline-based egimen. Patients with known cardiovascular disease or with high-risk features were excluded. Cardioprotective therapy [bisoprolol(B), Ramipril(R), or B+R], or placebo(P) were administered for 1 year since the initiation of chemotherapy or until the end of trastuzumab therapy in the case of HER2-positive patients. The drugs were systematically titrated up to the target daily dose of B (5 mg OD) and R (5 mg, OD) if tolerated. The primary endpoint was defined as the detection of any subclinical impairment (worsening ≥10%) in echocardiographic 3-dimensional left ventricular ejection fraction(3DLVEF) and global longitudinal strain(GLS) at the end-of-therapy (EOT) and at a 2-year follow-up (EOF). Echocardiographic measures of RV function (diastolic basal diameter, fractional area change(FAC), tricuspid annular plane systolic excursion(TAPSE), tissue Doppler-derived tricuspid lateral annular systolic wave velocity(S’RV) were analyzed. Results 262 women (median age, 48 years; range, 24-75 years) were enrolled and treated. We analyzed 222 patients who had completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor, and cardiovascular profiles were similar between arms. All patients received at least 1 cycle of anthracyclines (range 1-6) and 97% at least three cycles; 217 patients received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 with adjuvant endocrine therapy, and 124 had postoperative radiation therapy. At EOF 3DLVEF decreased by -10.5% in the P arm, by -3.0%, -2.4%, and -3.6% in the R, B, and R+B arms, respectively (P<0.001). At EOF GLS decreased by -13.1% in the P arm, by -3.6%, -3.0%, and -4.2% in the R, B, and R+B arms, respectively (P<0.001). At EOF the RV diameter increased by 6.7%, and FAC, TAPSE, and S’RV reduced by 10.5%, 9.6%, and 12.2%, respectively, in the P arm. In the drug arms, the changes in RV diameter, FAC, TAPSE, and S’RV were significantly less (Table and Figure). Conclusion Chemotherapy causes similar damage to the left and right ventricular function in breast cancer patients. Cardioprotective therapy significantly reduced both LV and RV damage in the low-risk patients of the SAFE study.TableFigure

Personalized treatment in localized pancreatic cancer

SummaryThe treatment elements used for pancreatic ductal adenocarcinoma (PDAC) include surgical resection, systemic cytotoxic agents, and targeted drugs. For second- and third-line therapies in PDAC, approximately 15% of patients have actionable mutations although only 2.5% receive matched targeted treatment but with a significant improvement in survival of around 16 months. For the majority of PDAC patients the current most effective strategy is surgical resection of the primary tumor and systemic combination chemotherapy. The chemotherapy regimens and the order of delivery relative to the resection reference point have been based to a large extent on randomized trials using a newly developed empirical staging (Em) system. Although the reductionist TNM based AJCC and UICC systems work well for pathology staging, they are less accurate and less manageable for treatment decision-making. This Em system defines locally resectable (EmR), borderline resectable (EmBR), and unresectable (EmUR) stages, plus the emerging entity of oligometastatic disease (EmOm). For EmR patients, 6 months of adjuvant chemotherapy achieves 5‑year survival rates of 30–50%. In EmBR short-course (2 months) neoadjuvant plus 6‑month adjuvant chemotherapy increases 12-month survival rates to around 77%, compared to 40% for upfront surgery, despite resection rates of 64–85% and 75%, respectively. Longer-course (4 months) neoadjuvant chemotherapy has also been shown to achieve an 18-month overall survival of 67%. In EmUR, induction therapy (3–6 months) may result in resections rates of 20–60% with significantly improved survival rates compared to no resection. For all stages including the polymetastatic (EmPm) setting, patients with good performance status receive combination chemotherapies based on either oxaliplatin (FOLFIRINOX or NALIRIFOX) or gemcitabine (GEM-CAP, or Gem-NabP). Molecular subtypes (Moffitt, Collisson, Bailey, and Cheng-Sen-Yue) are shown to be associated with treatment responses. Transcriptomic signatures have also been developed as classifiers for determining either oxaliplatin- or gemcitabine-based therapies (PurIST, Tiriac, GemPred+, and ESPAC) and are being evaluated in various studies. Most notably the ESPAC transcriptomic signature is being used as the treatment classifier in the experimental arms of the randomized ESPAC6 adjuvant trial in EmR patients and the ESPAC7 induction therapy trial in EmUR patients. Genomic and transcriptomic profiling at baseline and over time is an integral part of ESPAC6/7 to deepen our understanding of tumor plasticity during the course of therapy, identifying the intrinsic (persister cell) and acquired (genetic) tumor plasticity evolving over time and in reaction to different therapies in order to enable a scientific approach to overcoming clonal-resistance clades.

Doppler Ultrasound Assessment of Tumor Vascularity in Locally Advanced Breast Cancer at Diagnosis and following Primary Systemic Chemotherapy.

The primary goal of this research is to compare the morphological response, as determined by clinical and sonographic examination, to the gold standard, histology, in assessing the effectiveness of major systemic chemotherapy in patients with locally advanced breast cancer (LABC). During the check and before each example of chemotherapy (FAC schedule), 54 patients with privately progressed, non-metastatic breast disease underwent a comprehensive clinical assessment, ultrasonography of the breast and axillae, and assortment and spooky Doppler appraisal to evaluate response to therapy. In 90% of instances, Doppler provided early insight into how a patient might respond to treatment. Disappearance of all vascular signals inside the tumor was shown to be the strongest predictor of full pathological response. Patients with LABC may benefit from using color Doppler to determine how well chemotherapy is working.

Neoadjuvant therapy for pancreatic cancer.

Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4-6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.

Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma.

To evaluate the efficacy and toxicity of intravitreal carboplatin plus melphalan for the treatment of vitreous seeds in eyes with retinoblastoma (RB). This retrospective series at a tertiary referral center included 22 consecutive RB patients who had received intravitreal carboplatin (16μg per 0.05ml) combined with melphalan (30μg in 0.03ml) [IVi (Ca-Me)] for treatment of vitreous seeds. Tumor control and drug toxicities were recorded. There were 22 eyes of 22 patients, divided into primary group (n = 13) without history of previous intravitreal chemotherapy (IViC) and refractory group (n = 9) with history of previous IViC using melphalan and/or topotecan. The demographics and clinical findings of the primary and refractory groups did not differ significantly. The 6-month follow-up revealed complete vitreous seed control (77% vs. 89%, p = 0.47). Vitreous seed recurrence was detected in 1 eye of each group at 6months. During the next 18-month follow-up period, no recurrence of seed was observed. The response to IVi (Ca-Me) was not significantly influenced by previous IViC (p = 0.70), primary systemic or intra-arterial chemotherapy (p = 0.45), or the type of regression (p = 0.35). The most common tumor treatment complications were retinal detachment (RD) (n = 2), early hypotony (n = 2) and late hypotony (n = 4, unrelated), cataract (n = 2), and severe pigment dispersion (n = 1). Enucleation was performed in 8 eyes, for total RD (n = 1), phthisis bulbi (n = 5), and extensive solid tumor recurrence (n = 2). There was no case of orbital invasion, systemic metastasis, or death. Based on this interventional case series for primary and refractory vitreous RB seeds, carboplatin plus melphalan therapy may be effective with few toxic side effects.

Next Generation Sequencing of Reactive Stroma and Residual Breast Cancer Cells in Tumor Bed after Neoadjuvant Chemotherapy.

Primary systemic or neoadjuvant chemotherapy of breast cancer has become a standard therapy option in locally advanced or predefined intrinsic subtypes such as triple negative or Her2 positive breast cancer. Neoadjuvant chemotherapy can result in complete pathological response without residual tumor cells (tumor bed) or partial response and non-response with different amounts of reactive stroma and residual tumor cells. The interaction between therapy regimens and tumoral driver mutations have been extensively studied, although the reactive stroma of the tumor bed received less attention. In this study, we characterized the mutational status of residual breast cancer cells and reactive tumor stroma devoid of residual tumor cells in partial or non-responders using next generation sequencing. Twenty-one post-therapeutic breast surgical specimens after neoadjuvant chemotherapy underwent pathogenic driver-mutation screening using microdissected residual breast cancer cells and in reactive stroma adjacent to tumor bed areas. In reactive stroma, no mutations could be validated. In residual breast cancer cells, mutations were detected in sixteen of twenty-one cases (76%). In nine of these twenty-one cases (43%), pathogenic driver mutations (PIK3CA, PTEN, TP53, FN1, PLAG1) were identified. Pathogenic driver-mutations are exclusively restricted to residual carcinoma cells and are absent in reactive stroma independently from intrinsic breast cancer subtypes or tumor stage. These data suggest that the absence of pathogenic mutations in a tumor bed without residual tumor cells may have prognostic implications after neoadjuvant chemotherapy.

Novel scoring system guiding the incorporation of adjuvant RT for neuroendocrine neoplasms treated with surgical resection followed by chemotherapy.

This study aimed to investigate the role of adjuvant radiotherapy (RT) in neuroendocrine tumors (NET) treated with primary resection and systemic chemotherapy and guide to incorporate adjuvant RT based on individualized prediction. We identified 4324 eligible patients using the SEER database. The most common histology was small cell carcinoma (SCC), followed by neuroendocrine carcinoma and carcinoid tumor. As the patients treated with RT were not randomly assigned, we performed propensity score matching (PSM). RT was administered to 1693 (39.2%) patients who had more unfavorable features [higher proportion of SCC, N2/3 stage, and poorly/undifferentiated (PD) tumors]. After PSM, old age, male sex, SCC, advanced T or N stage, PD tumors, large tumor size, and no use of RT were all significantly associated with a poor prognosis. After multivariate analysis, the survival benefit of RT was preserved (HR 0.82, 95% CI 0.73‒0.91, p < 0.001). Exploratory analysis suggested that primary site, PD tumors, SCC, tumor size < 2cm, or LN negativity were the factors for which adjuvant RT appeared desirable. Further, we proposed a novel scoring system using aforementioned factors; site-thorax/genitourinary, PD tumor, tumor size < 2cm, LN negativity. Based on individually calculated scores, we found that RT significantly increased survival in patients with scores of 2-4 but not in those with scores of 0-1. Our study highlights the necessity of guiding adjuvant RT for these rare types of cancer. We proposed a novel scoring system to carefully recommend RT in selected patients.

Comparison of atezolizumab plus bevacizumab and lenvatinib in terms of efficacy and safety as primary systemic chemotherapy for hepatocellular carcinoma.

Atezolizumab plus bevacizumab and lenvatinib have each shown efficacy as primary systemic chemotherapies for hepatocellular carcinoma (HCC) in clinical trials. However, comparative trials of these two treatments have not been conducted. This study aimed to compare the therapeutic outcomes of these two treatments. This prospectively registered multicenter study analyzed 272 patients with HCC who received atezolizumab plus bevacizumab (the Atezo+Beva group; n=90) or lenvatinib (the Len group; n=182) as primary systemic chemotherapy. After propensity score matching (PSM), 66 patients were assigned to each group. After PSM, the median progression-free survival (PFS) was significantly longer in the Atezo+Beva group than in the Len group (8.8 vs. 5.2months; p=0.012). No significant differences were noted between the two groups in terms of median overall survival (not reached vs. 20.6months; p=0.577), objective response rates (43.8% vs. 52.4%; p=0.330), and disease control rates (76.6% vs. 82.5%; p=0.404). The percentage of patients with modified albumin-bilirubin grades of one or 2a was maintained during treatment in the Atezo+Beva group but decreased over time in the Len group. The rate of discontinuation due to adverse events (AEs) was lower in the Atezo+Beva group than in the Len group (12.1% vs. 28.8%; p=0.018). Atezolizumab plus bevacizumab showed prolonged PFS, maintained hepatic reserve, and had lower rates of severe AEs compared with that on using lenvatinib as primary systemic chemotherapy for HCC.

Is There a Role for Perioperative Radiotherapy in Surgically Resected Stage IV Rectal Cancer? A Propensity Score Matched Analysis

This study aimed to determine whether perioperative radiotherapy (RT) improves outcomes in stage IV rectal cancer patients treated with primary surgical resection and systemic chemotherapy and to identify predictive factors for selection of patients for these approaches.We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed between 2010 and 2015 with stage IV rectal cancer, but without brain or bone metastases. After applying the exclusion criteria, a total of 26,132 patients were included in the analysis; propensity score matching was used to balance their individual characteristics.Overall, 3283 (12.6%) patients received perioperative RT; the 3-year overall survival (OS) rates were 43.6% in the surgery group and 50.5% in the surgery with RT group (P < 0.001). The survival benefit of RT was maintained after propensity score matching and multivariate adjustment (HR 0.70, 95% CI, 0.66-0.81, P < 0.001). Interaction testing of the prognostic variables revealed a significant interaction between RT and the presence of lung metastasis (P < 0.001): the benefit of RT was observed only in patients without lung metastases (3-year OS 52.1% vs. 44.1%, P < 0.001), but it was observed regardless of liver metastases. Additionally, we developed a web-based calculator (http://bit.do/mRC_surv) to provide individualized estimates of OS benefit based on the receipt of perioperative RT.Perioperative RT significantly improved OS rates, especially in patients without lung metastases. We successfully developed a nomogram and web-based calculator that could predict survival benefit with the addition of RT for these patients.

Is There a Role for Perioperative Pelvic Radiotherapy in Surgically Resected Stage IV Rectal Cancer?: A Propensity Score-matched Analysis.

This study aimed to determine whether perioperative pelvic radiotherapy (RT) improves outcomes in stage IV rectal cancer patients treated with primary surgical resection and systemic chemotherapy and to identify predictive factors for selection of patients for these approaches. We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed between 2010 and 2015 with stage IV rectal cancer, but without brain or bone metastases. After applying the exclusion criteria, a total of 26,132 patients were included in the analysis; propensity score matching was used to balance their individual characteristics. Overall, 3283 (12.6%) patients received perioperative RT; the 3-year overall survival (OS) rates were 43.6% in the surgery group and 50.5% in the surgery with RT group (P<0.001). The survival benefit of RT was maintained after propensity score matching and multivariate adjustment (hazard ratio: 0.70; 95% confidence interval: 0.66-0.81; P<0.001). Interaction testing of the prognostic variables showed a significant interaction between RT and the presence of lung metastasis (P<0.001): the benefit of RT was observed only in patients without lung metastases (3 y OS 52.1% vs. 44.1%, P<0.001), but it was observed regardless of liver metastases. In addition, we developed a web-based calculator (http://bit.do/mRC_surv) to provide individualized estimates of OS benefit based on the receipt of perioperative pelvic RT. Perioperative pelvic RT significantly improved OS rates, especially in patients without lung metastases. We successfully developed a nomogram and web-based calculator that could predict survival benefit with the addition of RT for these patients.

The Predictive Value of the Eighth Edition of the Clinical TNM Staging System for the Likelihood of Eye Salvage for Intraocular Retinoblastoma by Systemic Chemotherapy and Focal Therapy.

The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) cTNM staging is emerging as a universal staging for all cancers, including retinoblastoma. Here we evaluated the predictive value of the eighth edition AJCC/UICC cTNM staging in comparison with the International Intraocular Retinoblastoma Classification for eye globe salvage by primary systemic chemotherapy and focal therapy (CRD) using logistic regression model for the probability of treatment failure. The eye salvage rate for 565 treated eyes was 95% (n=139/147) for T1 tumors (98% for T1a and 93% for T1b), 56% (n=230/410) for T2 (81% for T2a and 53% for T2b), and 0% for T3 tumors, and was 98%, 93%, 76%, and 44% for group A, B, C, and D tumors, respectively. As estimated by odds ratios, T2 were 13.6-fold more likely to fail treatment than T1, and T1b, T2a, and T2b were 2.8-, 9.4-, and 35.1-fold more likely to fail treatment than T1a, respectively. Group B, C, and D tumors were 2.8-, 12.7-, and 50.1-fold more likely to fail treatment than group A tumors, respectively. Eye salvage rate was 62% for eyes with focal seeds (3 mm close to the tumor), and 42% for eyes with diffuse seeds (clouds more than 3 mm from tumor edge) (P<0.0001). Both, the eighth edition cTNM classification and the International Intraocular Retinoblastoma Classification systems, can effectively predict eye salvage rates for retinoblastoma by CRD. Eyes with higher cT stages are more likely to experience treatment failure. Because the cT2b group is very heterogeneous, our findings suggest further division of this group based on the severity of vitreous/subretinal seeds, this should be revised in the next edition of cTNM system.

Clinical characteristics and prognostic factors of colorectal cancer patients with ovarian metastasis: a multicenter retrospective study.

As a kind of secondary tumor of the ovary, ovarian metastasis from colorectal cancer (OMCRC) happens rarely. Prognostic factors of OMCRC are still undetermined. This study was conducted to analyze clinical characteristics and prognostic factors of OMCRC patients. Data of patients with OMCRC were collected retrospectively from four large-capacity hospitals in China. Kaplan-Meier method was applied to estimate disease-specific overall survival (OS), and multivariate Cox regression analysis was used to identify prognostic factors. A novel nomogram was developed to estimate individual survival probability, whose performance was internally validated using concordance index (C-index) and calibration curve. Totally, 162 cases were eligible, with a median age at diagnosis of 49years old. The median size of ovarian metastases was 9.0cm (95% CI: 8.5-10.4cm). 93.8% of patients received surgery of ovarian metastases. Median time from CRC diagnosis to metachronous ovarian metastasis was 13.0months (95% CI: 13.5-17.7months). Median OS after ovarian metastasis diagnosis was 26.0months (95% CI: 22.3-29.7months). Integrating univariate and multivariate analyses, eight factors (including age, menopausal status, primary tumor location, N stage of primary tumor, surgery of primary tumor, differentiation grade, bilateral metastasis, and systemic chemotherapy) were used to develop a novel nomogram, with a C-index of 0.65 (95% CI: 0.595-0.705). Calibration curves indicated relatively good agreement between predicted and actual survival. This nomogram could be a promising tool to help clinicians to estimate individual survival outcome of patients with OMCRC. Further study is warranted to validate the practicality of this model.

Casuistics of primary metastatic ovarian cancer in pregnancy

Malignancies during pregnancy are usually treated similarly to the malignancies in non-pregnant patients. Results of controlled therapeutic trials are typically not available. However, registered studies associated with some of the most common malignancies exist. In case of ovarian cancer, due to its rarity – especially with the primary metastatic cases – only individual case reports are available. The article presents a case with par aortal abdominal, thoracic and cervical lymph node metastasis in a 33-years-old pregnant female. She was treated with primary systemic chemotherapy since early pregnancy. At 32 weeks of gestation, the patient gave birth to a girl (1460g) by caesarean section. Subsequently, the patient received 3 more cycles of chemotherapy with carboplatin/paclitaxel and bevacizumab for 30 months as well as letrozole maintenance therapy. Three years after the initial diagnosis, complete instrumental assessment showed unremarkable results without tumour recurrence.

Clinicopathological characteristics, practical treatments, prognosis, and clinical issues of older breast cancer patients in Japan.

Minimal data are available to support the clinical management of older breast cancer patients. Consequently, the standard of care remains unclear. Our aim was to clarify the clinicopathological characteristics, practical treatments, and prognosis of older Japanese breast cancer patients and discuss clinical issues. We reviewed 132,240 cases, diagnosed between 2004 and 2011, from the Japanese Breast Cancer Registry. Focusing on older patients, we compared data among three age groups: 75years and over (n = 27,385), 65-74years (n = 43,839), and 55-64years (n = 61,016). Data revealed the proportions of mucinous and apocrine carcinoma were higher in older patients, and they more frequently had clinical stage II and III cancer. Their ER-positive rates were higher, in contrast to the lower HER2-positive, breast-conserving surgery (BCS), post-BCS irradiation, and adjuvant chemotherapy rates. Almost half of the older patients who underwent chemotherapy received CMF or oral 5FU, during hormone therapy, Tamoxifen was administered more frequently. The overall survival rate decreased with age, but the breast cancer-specific survival (BCSS) at 5years remained similar. The rate of other cause of death in the oldest group was about a half, and more than double that in those aged 55-64years. We showed clinical data of older breast cancer patients in Japan. Their disease was more advanced at the time of diagnosis, post-BCS irradiation and primary systemic chemotherapy were omitted more frequently, and overall, BCSS was similar among age categories, although the rate of other causes of death was higher.

Was ist neu bei der Diagnostik und Therapie des Mammakarzinoms? – Aktuelle Standards in der Behandlung von Brustkrebs

Breast cancer is the most frequently diagnosed type of cancer in women and there are continuously new findings in research for further treatment approaches. Mammography is already a well-established prevention method in Germany for women aged 50-69, reducing mortality rates significantly. The benefit of extending the screening period including women older than 70 years has been proven recently. Intensive research in hereditary breast cancer makes it possible to identify high risk patients and include them to a more frequent screening program with additional MRI. In early as well as in advanced stages of breast cancer the treatment should be as targeted and as noninvasive as possible. After neoadjuvant therapy a mastectomy is needed less frequently and axillary lymph node dissection can be limited to rare cases. Molecular subtyping allows more individualized treatment in curative and palliative intention. BIA-ALCL is an uncommon and highly treatable T-cell lymphoma associated with textured silicone or saline filled breast implants. Despite increasing incidence the usage of those implants is possible - but only after adequate information. Due to new insights into the biology of breast cancer the period of follow-up care has been expanded to ten years. The detection of an ESR1 mutation could possibly be used as a predictive marker regarding endocrine therapy in the future. Furthermore, there are promising results for blocking the PD-1 axis in primary systemic chemotherapy for triple-negative breast cancer.

CONVERSION SURGERY FOR STAGE IV GASTRIC CANCER. LITERATURE REVIEW AND OWN EXPERIENCE

Metastatic gastric cancer is associated with poor prognosis despite of advances in chemotherapy and surgery. According to current clinical guidelines surgical treatment for stage IV gastric cancer patients is indicated only for urgent complications. New approach for the management of patients with initially unresectable or metastatic gastric cancer includes primary systemic chemotherapy and following surgical resection if the patients are able to undergo complete resection. This approach is known as conversion surgery. In the review with presentation of own experience the results of conversion surgery for gastric cancer with distant metastases of various localization (liver, paraaortic lymph nodes and peritoneum) were reported. These results allow to define indications for this treatment strategy. 15 conversion surgery cases are presented, 12 of them were combined with HIPEC or PIPAC. Median progression-free survival was 18 months. Conclusion: literature analysis and own experience have shown that conversion surgery after chemotherapy increases the overall survival of patients with oligometastatic gastric cancer who underwent complete resection as compared with palliative chemotherapy. However the clear selection criteria for conversion surgery are needed from randomized controlled trials.

Landscape of systemic therapy for ovarian cancer in 2019: Primary therapy.

According to the statement from the 5th Ovarian Cancer Consensus Conference in 2015, the primary systemic chemotherapy for advanced ovarian cancer is a combination of paclitaxel plus carboplatin administered every 3weeks (PCq3w). Optional alternatives include weekly dose-dense paclitaxel, in combination and maintenance therapy with bevacizumab, and intraperitoneal chemotherapy. Since then, in addition to the PCq3w strategy, there has been emerging new evidence, especially for poly(adenosine diphosphate-ribose) polymerase inhibitors. Moreover, there are multiple randomized, phase 3 trials testing the addition of antiangiogenic and/or immune checkpoint inhibitors in this patient population. In this article, current and future perspectives of systemic chemotherapy for advanced ovarian cancer are discussed.

238P - Elderly patients in the Japanese breast cancer registry

BackgroundAim: To clarify the clinicopathological characters and treatments and prognosis in elderly breast cancer patients using the Japanese Breast Cancer Registry (JBCR) system. MethodsWe reviewed data from JBCR, which is the nation-wide registry of newly diagnosed and operated primary breast cancer patients in Japan. To clarify its characteristics, we compared elderly patients aged 75 and over (elderly) with aged from 65 to 74 (young-old; y-o) and that from 55 to 64 (post-menopausal; p-m), respectively. ResultsIn total 132,240 cases diagnosed between 2004 and 2011 were reviewed (elderly; n=27,385, y-o; n=43,839, p-m; n=61,016). In histology, the proportion of mucinous carcinoma and apocrine carcinoma were higher in elderly (6.1%, 1.8%, y-o; 3.5%, 1.7%, p-m; 1.8%, 1.3%, respectively). Patients with clinical stage II and III were more frequent in elderly (45.1%, y-o; 39.0%, p-m; 39.8%). ER -positive rate was higher (76.8%, y-o; 76.3%, p-m; 72.7%) and HER2-positive rate was lower in elderly (10.5%, y-o; 12.8%, p-m; 18.6%, p<0.001). As for surgery, the rate of breast conserving surgery (BCS) was lower in elderly (46.4%, y-o; 55.0%, p-m; 59.6%), and the rate of no surgery for axilla was higher in elderly (18.4%, y-o; 5.9%, p-m; 4.8%, p<0.001). Irradiation after BCS was performed only in 41.3% of elderly patients, whereas y-o and p-m were 75.9%, 83.0%, respectively. Adjuvant chemotherapy was performed only in 10.8% of elderly patients, y-o and p-m were 31.8%, 46.2%, respectively. Half of elderly patients (49.8%) who underwent chemotherapy were given CMF or oral 5FU. As for hormone therapy, Tamoxifen was used more frequently in elderly (18.1%, y-o; 10.6%, p-m; 9.7%). The 5 years-survival analysis is shown in Table.Table238PTableAge≧7565-7455-64Distant disease-free survival (%)93.194.393.1Overall survival (%)84.393.794.4Breast cancer-specific survival (BCSS) (%)94.296.795.9Other disease death (%)48.035.820.6 ConclusionsElderly patients suffered from more advanced disease at the time of diagnosis. Irradiation after BCS and primary systemic chemotherapy was more frequently omitted in the elderly patients. Overall, BCSS was similar among ages, but the rate of other causes of death was higher in elderly patients. Legal entity responsible for the studyThe authors. FundingJapanese Breast Cancer Society. DisclosureAll authors have declared no conflicts of interest.