Financial toxicity and patient experience associated with financial burden of molecular-targeted and immune therapies for cancer: an observational study under public health insurance.

BACKGROUND: Financial burden of cancer treatment can negatively affect patients and their families. This study aimed to evaluate the financial toxicity of patients treated with molecular-targeted and immune therapies and explore the relationship between financial toxicity and patient experiences associated with the financial burden of cancer treatment. METHODS: This anonymous, self-administered questionnaire survey conducted across nine hospitals in Japan included patients aged 20-60 years who were receiving molecular-targeted agents or immune checkpoint inhibitors for any type of cancer for ≥ 2 months. Financial toxicity was evaluated using the COmprehensive Score for Financial Toxicity (COST). Patient experience was examined using 11 items based on previous studies. Independent factors related to financial toxicity were explored using multiple regression analyses. RESULTS: The mean COST score was 17.0 ± 8.4, and 68 (49.3%) participants reported COST scores at or below the cutoff point. The factors contributing to financial toxicity were "hesitation regarding continuing treatment based on finances" (sß = - 0.410, p < 0.001), "cutting through my deposits and savings" (sß = - 0.253, p = 0.003), and "reducing spending on basics like food or clothing" (sß = - 0.205, p = 0.046) along with comorbidities (sß = - 0.156, p = 0.032). CONCLUSION: Patients receiving molecular-targeted and immune therapies are at risk of experiencing profound financial toxicity and a reduced quality of life. The independently related factors that we identified have the potential to serve as indicators of profound financial toxicity and the need for specialized intervention.

Overcoming the polyethylene glycol dilemma via pathological environment-sensitive change of the surface property of nanoparticles for cellular entry.

Modification with polyethylene glycol (PEG) is currently considered an important strategy for anti-cancer drug delivery, because PEGylated-nanoparticles would be effectively delivered to tumor tissue by enhanced permeation and retention effects. However, PEGylation suppresses the cellular uptake of nanoparticles (NPs) to target cells (known as the PEG dilemma). Here, we propose a novel strategy, namely conferring a pathological environment-sensitive property of nanoparticles for overcoming the PEG dilemma. Specifically, although nanoparticles have an overall negative surface charge to avoid interactions with biogenic substances in blood circulation, inversion of surface charge (to positive) at the pH of the tumor microenvironment may allow the nanoparticles to be taken up by cancer cells. To prove this concept, charge-invertible nanoparticles modified with novel slightly acidic pH-sensitive peptide (SAPSP-NPs) were developed. The negatively-charged SAPSP-NPs were delivered to tumor tissue, and were successfully taken up by cancer cells upon inversion of the surface charge to positive at intratumoral pH. SAPSP-NPs may serve as an alternative carrier to the PEGylated NP for anti-cancer drug delivery.

Paratesticular myxoid/round cell liposarcoma harboring type 3 DDIT3-FUS fusion gene: report of a very rare case.

Myxoid/round cell liposarcomas are rare mesenchymal neoplasms. They preferentially occur in the lower extremity, and most of them have type 1 or type 2 DDIT3-FUS fusion gene. We report here a very rare case of myxoid/round cell liposarcoma of the paratesticular region with type 3 DDIT3-FUS fusion gene. A 46-year-old Japanese man noticed a gradually enlarged intrascrotal mass without pain. Surgical resection of 3.4 cm × 2.1 cm oval mass was carried out, and it was located in the right paratesticular region apart from the spermatic cord and epididymis. Histological examination of the tumor revealed ovoid cell proliferation with anastomosing vascular network and scattered lipoblasts. Genetic analysis elucidated that the tumor had a chromosomal translocation, type 3 DDIT3-FUS chimeric gene. The tumor was definitely diagnosed as myxoid/round cell liposarcoma of the paratesticular region.

Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case.

We herein report the case of a 48-year-old Japanese female with retroperitoneal epithelioid hemangioendothelioma (EHE), a rare malignant vascular tumor of intermediate grade. She was referred to our hospital because a retroperitoneal tumor was found during a medical checkup, in which strong accumulation of (18)F-fluorodeoxyglucose (FDG) was observed by (18)F-FDG-positron emission tomography (PET). A histological examination of the resected tumor revealed that it consisted of large epithelioid cells with vesicular nuclei, and clear cells with vacuolated cytoplasm and intracytoplasmic lumina. These cells expressed CD31 and vimentin, and the final pathological diagnosis was EHE. Postoperative surveillance with FDG-PET revealed distant metastasis in Virchow's lymph node 7 months after the operation. After dissection of the metastatic lymph node, the patient has been free from recurrence for 13 months. Close follow-up with FDG-PET seemed to be useful for surveillance of the recurrence of this tumor with unpredictable behavior, making an early treatment for the recurrent lesions possible.

Characterization of novel germline c-kit gene mutation, KIT-Tyr553Cys, observed in a family with multiple gastrointestinal stromal tumors.

We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c-kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib, another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family.

Primary carcinoid tumor of the urinary bladder with prominent subnuclear eosinophilic granules.

Primary carcinoid tumor of the urinary bladder is a very rare neoplasm. We report here a case of primary carcinoid tumor of the urinary bladder with an unusual cytological feature in a 72-year-old Japanese man. A bladder polypoid mass was incidentally found by ultrasonography during the follow-up of a benign prostate hyperplasia. Histological examination of the transurethrally resected tissue revealed that the upper part of the mass was a tumor showing tubuloglandular anastomosing structures. Most of the tumor cells had peculiar subnuclear eosinophilic granules. The features of the granules were reminiscent of those observed in neuroendocrine cells of the intestine. The tumor cells were immunohistochemically positive for chromogranin A and synaptophysin. The tumor was diagnosed as carcinoid tumor of pure form of the urinary bladder. The lower part of the mass showed the findings of glandular cystitis, as its coexistence with carcinoid tumors of the bladder has often been described in previous reports.

New double embedding technique for specimens of endoscopic submucosal dissection using agarose: comparison with other media.

AIMS: Procedure of endoscopic submucosal dissection (ESD) has been introduced widely for treatment of early gastric cancers. For such specimens, accurate pathological diagnosis, especially concerning depth of the invasion and exposure to margins, is essential to decide on the necessity of additional treatment. Therefore, easy and reliable tissue-processing method for multiple cut specimens is needed. The authors report here a new double embedding technique for specimens of ESD. METHODS: Formalin-fixed whole specimen was superficially wrapped by agarose (the first embedding), and the tissue-agarose block was cut at 2-3 mm intervals. Each cut specimen was laid down with 90° rotation. This procedure permitted 'on edge' embedding of thin tissues in paraffin (the second embedding) and subsequent preparation of perpendicular section to the tissue surface. The authors compared the handleability and stainability among several media including various types of agar, agarose and gelatin for first embedding. A survey by questionnaire was carried out on handleability and/or impression on various tissue-processing steps from pathology technicians. RESULTS: Among the media examined, agarose showed the best solubility in water and the best transparency on several representative stainings. According to the survey, pathology technicians seemed to feel that the present method was better than the usual tissue processing method, especially in shortened time consumption and accuracy of alignment of multiple tissues for ESD specimens. CONCLUSIONS: The present new double embedding technique using agarose provides not only an easy and reliable embedding procedure for technicians but also accurate and exact diagnosis for pathologists.