Study protocol of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with Oxaliplatin and 5-fluorouracil/Folinic acid followed by curative surgical resection in patients with hepatic Oligometastatic adenocarcinoma of the pancreas (HOLIPANC)

Background According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. Methods In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. Discussion This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Trial registration numbers EudraCT 2019–002734-37; NCT04617457.

Cascade Release Nanocarriers for the Triple-Negative Breast Cancer Near-Infrared Imaging and Photothermal-Chemo Synergistic Therapy

Triple-negative breast cancer (TNBC) has inadequate treatment approaches and a poor prognosis. It is urgent to develop new treatment approaches for TNBC. The combination of photothermal therapy (PTT) and chemotherapy is a very effective potential therapy for TNBC. However, asynchronous accumulation, unclear efficacy, and toxic side effects hinder the further promotion of this method. Therefore, we designed and constructed a new type of nanocarriers, the cascade release near-infrared imaging (NIFI) & thermal-chemo combination nanoparticles (CNC NPs), that can release drugs through the cascade of ultrasound triggering and pH responding to achieve the synchronous tumor accumulation, monitoring and synergistic treatment of two functional molecules. The key material of CNC NPs is the polydopamine (PDA), which, through self-assembling, forms a rigid shell that contains doxorubicin (DOX) and NIF fluorescent dye IR780 on the surface of the perfluorohexane (PFH) microbubbles. The results show that CNC NPs have a hollow core-shell structure with an average particle size of 97.3 ± 27.2 nm and have exceptional colloidal stability and photothermal conversion efficiency. The NPs can effectively perform cascade drug release through ultrasound triggering and pH responding. CNC NPs have good in vivo biological safety and excellent fluorescence imaging, drug delivery, and therapeutic abilities in the TNBC models. These results provide an experimental basis for the development of new clinical treatment methods for TNBC.

A 10-Year Evaluation of Short-Term Outcomes After Synchronous Colorectal Cancer Surgery: a Dutch Population-Based Study

Background Synchronous colorectal cancer (CRC) has been associated with higher postoperative morbidity and mortality rates compared to solitary CRC. The influence of improved CRC care and introduction of screening on these outcomes remains unknown. This study aimed to evaluate time trends in incidence, population characteristics, and short-term outcomes of synchronous CRC patients at the population level over a 10-year time period. Methods Data of all patients that underwent resection for primary CRC were extracted from the Dutch ColoRectal Audit (2010–2019). Analyses were stratified for solitary and synchronous colon and rectal cancer. Multilevel logistic regression analyses were used to determine factors associated with pathological and surgical outcomes. Results Among 100,474 patients, 3.1% underwent surgery for synchronous CRC. A screening-related decrease for surgically treated left-sided solitary and synchronous colon cancer and a temporary increase for exclusively right-sided colon cancer were observed. Synchronous CRC patients had higher rates of complicated postoperative course, failure to rescue, and mortality. Bilateral synchronous colon cancer was more often treated with subtotal colectomy (25.4%) and demonstrated higher rates of surgical complications, reinterventions, prolonged hospital stay, and mortality than other synchronous tumor locations. Discussion National bowel screening resulted in contradictory effects on surgical resections for synchronous CRCs depending on sidedness. Bilateral synchronous colon cancer required more often extended resection resulting in significantly worse outcomes than other synchronous tumor locations. Identification of low volume, high complex CRC subpopulations is relevant for individualized care and has implications for case-mix correction and benchmarking in clinical auditing.

Multiple primary malignancies among patients with advanced melanoma.

e22531 Background: Multiple primary malignancies (MPMs) describe two or more primary tumors arising in a synchronous or metachronous manner in the same individual. Patients with a primary cutaneous melanoma are at high risk of developing MPMs. While melanoma and other tumors are highly immunogenic and may cause immune suppression at the individual level, the molecular underpinnings of immune suppression among patients with MPMs remains to be elucidated. Here, we attempt to describe this rare, but unique group of patients who have both advanced melanoma and at least one other primary malignancy. Methods: Patients with advanced melanoma (stage III-IV disease) and at least one other non-melanoma cancer were identified. Synchronous tumors were defined as those occurring within 6 months of the first primary cancer. Metachronous tumors were defined as those occurring at least 6 months after the first primary cancer. Patients who had melanoma first, before a second cancer, and those who had a prior other cancer first, followed by melanoma were included. Overall survival (OS) describes the time from diagnosis of the first primary cancer to death due to any cause. Two-sample t-tests were used to compare OS among these groups with statistical significance if p < 0.05. Results: Eleven patients with MPMs including advanced melanoma were identified. Advanced melanoma was the first primary tumor in 5 patients and the second primary in 6 patients. A synchronous second primary was observed in 4 patients, whereas a metachronous second primary was observed in 7 patients. The median time between the diagnosis of the first primary cancer to the second primary was 21 months and the median time between the diagnosis of a second primary to a third primary was also 21 months. The median OS for all patients was 73 months. The median OS for synchronous MPMs and metachronous MPMs were 64.5 months and 82 months, respectively (p = 0.013). For patients with melanoma as the first primary cancer, the median OS was 73 months, compared to 87 months when melanoma was the second primary cancer (p = 0.785). Among all 11 patients, two are deceased, while the remaining patients are under surveillance. Among the remaining 9 patients, 100% have no evidence of disease with respect to melanoma. Conclusions: Despite the favorable outcomes from early detection and the advanced treatments available such as immunotherapy, a robust treatment plan should be in place when advanced melanoma is diagnosed as a synchronous tumor or second primary cancer. Further research is warranted since there are no guidelines available for the treatment of MPMs.

Analysis of bilateral breast carcinomas:a profile of patients at a reference service

Objective: To select cases of bilateral breast carcinoma (BBC) of patients seen at Hospital de Clínicas of Paraná, besides recognizing clinical and family characteristics, histological and immunohistochemical pattern, and incidences of synchronic/metachronic tumor in these patients. Method: Observational and analytical study of BBC cases of patients treated at Hospital de Clínicas of Paraná, from 2003 to 2019, developed from the analysis of medical records. Result: A total of 42 patients with BBC were selected. The incidence of BBC was 3.64%. All patients were women, mostly of white skin color and postmenopausal, with an average age of 51.82 years. Half patients showed a positive family history for cancer, with breast cancer present in 46%, ovarian cancer in 16%, and other topographies in 68%. In this sample, the synchronous tumor was present in 55% of patients, and the metachronous tumor, in 45%. Regarding patients’ initial clinical staging, 61% had a locally advanced tumor at diagnosis. Both in the group of synchronic and metachronic tumors, the ductal subtype was the most frequent. Regarding the immunohistochemical subtype, patients in both groups had Luminal B tumors more frequently. In the group of metachronic tumors, the average time between the diagnosis of the first tumor and the second tumor was 5.68 years. Conclusion: In this sample, BBC is associated with a relevant family history, with a synchronic presentation pattern, from histology to ductal and immunohistochemistry to Luminal B as the most frequent.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research.

Clinically unsuspected primary hepatic mucosa-associated lymphoid tissue lymphoma collision with an intrahepatic cholangiocarcinoma: A case report and literature review

A synchronous tumor represents two histologically distinct neoplasms occurring at the same anatomic site, each displaying a distinct tumorigenesis pathway; they can be primary, secondary, or a mixture. The occurrence of an adenocarcinoma and lymphoma has been reported in gastrointestinal and pulmonary sites; however, such a finding in hepatobiliary system remains elusive. Primary hepatic lymphoma is rare, while primary biliary mucosa-associated lymphoid tissue lymphoma is an even rarer event; hence, its collision with an intrahepatic cholangiocarcinoma could be entirely missed both in practice and in the literature. We herein reported a case of biliary mucosa-associated lymphoid tissue lymphoma occurring synchronously with an intrahepatic cholangiocarcinoma in a 78-year-old female following a biopsy-proven intrahepatic cholangiocarcinoma and hepatectomy. Microscopic examination identified atypical lymphoid population intermingled with this intrahepatic cholangiocarcinoma. An immunohistochemical panel uncovered an incidental mucosa-associated lymphoid tissue lymphoma occurring with this intrahepatic cholangiocarcinoma. This clinically missed entity led to comprehensive systemic investigation/staging, with subsequent detection of bone marrow involvement by stage IV lymphoma. This unique case highlights the importance of astute histomorphological evaluation and thorough ancillary studies in identifying a clinically unsuspected neoplasm in close contact with a known tumor.

Tumor sincrónico de endometrio y ovario. Patología infrecuente en ginecología oncológica

Endometrial cancer remains the most common gynecological tumor in women in the United States of America. The simultaneous finding of endometrial and ovarian neoplasm, as a synchronous tumor, accounts for about 5 - 10 % of endometrial and ovarian tumors. Therefore, is a rare entity. Consideration as restricted metastases or pseudometastasis to define the spread of this kind of tumor, is becoming more relevant nowadays thanks to the latest advances in the field of immunohistochemistry and molecular biology. In this article we present the case of a 57-year-old patient initially diagnosed with FIGO stage IIIA endometrial carcinoma; subsequently, it was a synchronous endometrial tumor stage IB and IC ovary, despite the presurgical suspicion of a metastatic tumor. Keywords: Endometrial Neoplasm, Ovarian Neoplasm, Synchronous Neoplasm, Multiple Primary Neoplasm, Neoplasm Metastasis.

Prognostic Factors of Sinonasal Squamous Cell Carcinomas Arising De Novo and From Inverted Papilloma

Background The prognostic factors and survival difference between inverted papilloma (IP)-associated sinonasal squamous cell carcinoma (SCC) and de novo SCC are unclear. Objective This study aimed to compare the clinical features and oncologic outcomes in patients with IP-associated SCC and de novo SCC; and additionally, to analyze the prognostic factors of the two types of SCCs. Methods Data from 173 SCC patients treated for IP-associated SCC (n = 89) and de novo SCC (n = 84), were reviewed retrospectively for demographic features, tumor characteristics, treatment modality, and clinical outcomes. 5-year overall survival (OS) and disease free survival (DFS) was analyzed using the Kaplan-Meier method, and Cox proportional hazards model was used to analyze factors influencing prognosis. Results A higher proportion of IP-associated SCC occurred in frontal and sphenoid sinus compared to de novo SCC. The two groups demonstrated similar 5-year OS and DFS (5-year OS: 63.3% and 55.4%, DFS: 45.4% and 50.1%, respectively). The metachronous tumor had a relatively better prognosis outcome than synchronous tumor and de novo SCC (5-year OS: 73.1%, 54.5% and 55.4%, respectively). Both groups showed similar loco-regional recurrence rates ( p > 0.05); however, de novo SCC tumors demonstrated an increased incidence of distant metastasis. Multivariate analysis indicated that age >70 years, advanced tumor stage and surgical margin were independent predictive factors for the risk of mortality (HR 2.047, 1.581 and 1.931, respectively). Conclusion IP-associated SCCs have an aggressive loco-regional tendency, whereas de novo SCCs have a higher aggressive distant metastatic propensity. Age, tumor stage and surgical positive margin are key factors for poor prognosis and should be routinely taken into consideration during treatment planning and subsequent surveillance.