Lives Embraced Through Memories

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23–4,993 days), and the median duration of patient follow-up was 256 days (range, 11–2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17–240 Gy2; α/β = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.

Low risk asymptomatic bone metastasis (LRABM) without gross osteolytic changes tends to be out of indication for radiotherapy. The aim of this study was to evaluate the time between the end of palliative radiotherapy of bone metastasis (BM) until the start of new pain, in patients with painful BM. Patients with BM were prospectively assessed for location and strength of pain every month for one year after radiotherapy. The correlation of pain relapse at irradiated site, and pain onset outside the irradiated site was evaluated with sex, age, primary tumor, pathology of tumor, visceral metastases, baseline scores for Eastern Cooperative Oncology Group performance status (PS), and baseline verbal rating scale (VRS). A hundred and thirty-two patients were included (79 males and 53 females). Median age was 66 years. Primary sites were lung (n=60), breast (n=17), colon (n=12), prostate (n=11), and others (n=33) (one patient had two primary sites). Median follow-up was 185 days. Pain relief was observed in 92 patients (86.0%). Out of them, pain progression was observed in 69.6%. Median time to pain progression was 75.5 days. Pain onset outside the irradiated site was observed in 57 patients (43.2%). Median time to pain onset was 109 days. Out of the 57 patients, 13 (22.8%) had LRABM which existed before the start of radiotherapy. There were 54 patients with LRABM in this study and because many patients had more than one LRABM, the total LRABM sites were 123. Out of them, pain onset was observed within one year after irradiation in 44 (36%) lesions. Median time to pain onset was 67 days, which was the shortest of the three: irradiated site, out of the irradiated site, and LRABM site. Risk factors for high probability of pain onset within one year in LRABM lesions were female sex (showing a trend in univariate analysis), and pelvic, skull and spine metastasis (significant in multivariate analysis). Time to pain onsets in LRABM are relatively short, especially in female patients with pelvic, skull and spine metastasis. In these patients, prophylactic radiotherapy could be an option to consider.

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Background/Objective: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. Materials and Methods: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. Results: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). Conclusion: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

To study tumour growth and metastasis in a rabbit metastatic breast cancer (MBC) model and find the most sensitive screening modality in monitoring tumour metastasis. The MBC model was established by injecting a VX2 tumour mass suspension into the mammary glands of 23 rabbits and was monitored by using physical examination, X-ray, MRI and hybrid PET/CT. Of all 23 rabbits, axillary lymph node metastasis was detected in 21 (91%) at day 33 after tumour inoculation, mediastinal node metastasis in five (22%) at day 42, abdominal node metastasis in two (9%) at day 48, lung metastasis in six (26%) at day 39, liver metastasis in three (13%) at day 48, and lumbar spine metastasis in one (4%) at day 51. Tumour invasion of pleura was found in one, stomach wall in one, and pleura and stomach concurrently in one rabbit. Sensitivity for detection of lymph node metastases was 78.6% (22/28) and 67.9% (19/28) with MRI and PET/CT, respectively; and sensitivity for detection of metastases in distant organs was 85.7% (12/14) and 71.4% (10/14), respectively. The MBC model used here exhibits fast tumour growth and extensive metastasis in a relatively short period. Its metastatic pattern is quite similar to that of human MBC and hence could be potentially used as a model for testing imaging modalities and translational research, e.g., MBC management. MRI is superior to PET/CT in monitoring tumour metastasis.

Peripheral T-cell lymphomas (PTCLs) are an uncommon and heterogeneous group of well-differentiated, post-thymic T-cell malignancies that can present in the skin as cutaneous T-cell lymphomas. In general, their prognosis is poor, and specific therapy is not well defined. We report the successful treatment of a patient with relapsed, refractory PTCL who after failing 13 standard single and multiple chemotherapy regimens and experimental agents had a dramatic prolonged response to diftitoxin denileukin (ONTAK ® ). This fusion protein, composed of diphtheria toxin coupled to interleukin-2, is approved for cutaneous T-cell lymphomas, including mycosis fungoides, and should be considered for treatment of the rare subset of peripheral T-cell lymphomas.

Establishment of a Novel Cell Line of Plasmablastic Lymphoma with Loss of p16 Tumor Suppressor Protein and Overexpression of MDR

The effect of chemotherapy on tumor heterogeneity and activation of the immune system in cancer is poorly understood. We present an unusual case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited spontaneous regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. The primary tumor was resected before chemotherapy treatment started. After 5 years of chemotherapy without response, treatment was stopped, the patient transitioned to best supportive care and was followed clinically with regular CA125 biomarker evaluation. During the course of 2 years of clinical follow up, CA125 decreased and computerized tomography (CT) scans revealed one regressing (right upper quadrant), one stable (liver), and two progressing (spleen and vaginal cuff) metastases. Due to abdominal discomfort, metastases were simultaneously resected. We performed: a) CT scan-based radiomics to anlayze tumor heterogeneity, b) exome sequencing to identify somatic mutations, predict neoepitopes, and estimate neoepitope depletion, and c) immunofluorescence staining to analyze immune cell infiltration on the primary and four metastatic tumors. We found that chemotherapy increases tumor heterogeneity, and metastases that developed after multi-line chemotherapy have a higher somatic mutation rate, more neoepitopes, and mutations in immune recognition molecules compared to metastases that appeared earlier. The right upper quadrant regressing and the liver stable metastases were infiltrated by CD4+ and CD8+ T cells. The vaginal cuff progressing metastasis was characterized by immune cell exclusion, while the spleen progressing metastasis was infiltrated only by CD8+ T cells. Finally, we detected neoepitope depletion only in the right upper quadrant regressing metastasis, potentially indicating an active immunoediting process. These findings indicate that multiple distinct tumor immune microenvironments can co-exist within a single individual, evidencing potential clinical challenges for the appropriate application of immunotherapy and chemotherapy combinations to overcome tumor heterogeneity at the genetic and tumor-microenvironment levels. Citation Format: Alejandro Jiménez-Sánchez, Harini Veeraraghavan, Yanyun Li, Hebert Alberto Vargas, Michael B. Gill, Kay J. Park, Oliver Zivanovic, Jason Konner, Jacob Ricca, Dmitriy Zamarin, Carol Aghajanian, Jedd D. Wolchok, Taha Merghoub, Evis Sala, Alexandra Snyder, Martin L. Miller. Heterogeneous fates of metastatic lesions linked to immune escape in an ovarian cancer patient. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B09.

Locally advanced gastro-oesophageal cancer: Recent therapeutic advances and research directions

Reports of Mesonephric-like adenocarcinoma (MLA) arising from other than the ovary and uterus are exceedingly rare. This report details two cases of MLA in patients with a history of endometriosis. One of these two cases is believed to be the first documented case of primary peritoneal MLA.The first case was a 64-year-old woman with a history of hysterectomy and oophorectomy for endometriosis. She presented with International Federation of Gynecology and Obstetrics (FIGO) stage IVB primary peritoneal MLA, diagnosed eight years later via CT-guided biopsy and immunohistochemistry. Despite multiple chemotherapy regimens, she died 13 months after initiation of treatment. The second case was a 72-year-old woman with a history of endometriosis, and she was diagnosed with FIGO stage IIIA1(i) ovarian MLA. She underwent complete cytoreductive surgery followed by adjuvant paclitaxel and carboplatin chemotherapy and remained recurrence-free for three years. A literature review of 66 reported cases of ovarian MLA was conducted to compare clinical characteristics, treatment, and prognosis. According to these findings, 55% were diagnosed at an early stage (FIGO I-II), and prognosis was generally favorable after complete surgical resection, but outcomes were poor for sub-optimally resected cases.These cases suggest a potential link between MLA development and a history of endometriosis, particularly after surgical intervention. The prognosis for MLA is highly dependent on achieving complete surgical resection. Advanced-stage primary peritoneal MLA has a poor prognosis, comparable to conventional primary peritoneal serous carcinoma. Given the difficulty of preoperative diagnosis, diligent follow-up is recommended for high-risk patients with a history of endometriosis. Future research is needed to establish effective treatments for advanced or recurrent disease.

Despite advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, with a poor prognosis at time of diagnosis. Research in PDAC has suggested that adaptive signaling in the tumor microenvironment may promote tumor proliferation and survival. Several FGFR fusion genes-specifically FGFR2-are involved with the creation and progression of cancer. These mutations are found in a variety of cancer types. This report presents a unique case of a young patient with stage IV PDAC with a known FGFR2 fusion. This molecular alteration afforded a remarkable response to FGFR inhibitor therapy, erdafitinib, after the patient experienced disease progression on multiple chemotherapy regimens.

Pancreatoblastoma in an Adult: Case Report and Review of the Literature

BACKGROUNDConventional therapies for primary plasma cell leukemia (pPCL) are usually ineffective, with a short remission time with the use of multiple myeloma medications, showing aggressiveness of pPCL. B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma (RRMM) with t(11;14). There are very few studies published on the use of venetoclax in pPCL without t(11;14). Similarly, histone deacetylase inhibitors are considered effective for the treatment of RRMM, but there are no reports on their use in pPCL.CASE SUMMARYA 57-year-old woman with severe anemia, thrombocytopenia, multiple bone destruction, impaired renal function, and 42.7% of peripheral plasma cells is reported. After multiple chemotherapy regimens and chimeric antigen receptor T-cell treatment, the disease progressed again. The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSIONThe success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

591 THE EFFECT OF PHOTOCHEMICAL INTERNALIZATION OF BLEOMYCIN IN THE TREATMENT OF UROTHELIAL CARCINOMA: AN IN VITRO STUDY

Thirty patients with relapsed Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) and autologous bone marrow transplantation. The median age of the patients was 28 years, and 18 were male. More than half had extranodal sites of relapse and constitutional symptoms. Most had been heavily pretreated with multiple salvage chemotherapy regimens and radiotherapy. At the time of transplantation, 23 patients were having progressive disease despite salvage chemotherapy. High-dose CBV chemotherapy induced complete responses in 15 patients and partial responses in 10 patients. Eleven patients are still in complete remission, 1 of whom has had an unmaintained remission for more than 44 months. Toxicity was moderate; all patients had severe myelosuppression requiring supportive therapy, and 1 patient failed to reconstitute her bone marrow. High-dose CBV chemotherapy and autologous bone marrow rescue proved to be effective as salvage therapy for a select group of heavily pretreated patients with relapsed Hodgkin's disease.