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Purpose: To evaluate the dosimetric effects of intrafraction baseline shifts combined with rotational errors on Four-dimensional computed tomography-guided stereotactic body radiotherapy for multiple liver metastases (MLMs). Methods: A total of 10 patients with MLM (2 or 3 lesions) were selected for this retrospective study. Baseline shift errors of 0.5, 1.0, and 2.0 mm; and rotational errors of 0.5°, 1°, and 1.5°, were simulated about all axes. All of the baseline shifts and rotation errors were simulated around the planned isocenter using a matrix transformation of 6° of freedom. The coverage degradation of baseline shifts and rotational errors were analyzed according to the dose to 95% of the planning target volume (D95) and the volume covered by 95% of the prescribed dose (V95), and related changes in gross tumor volume were also analyzed. Results: At the rotation error of 0.5° and the baseline offset of less than 0.5 mm, the D95 and V95 values of all targets were >95%. For rotational errors of 1.0° (combined with all baseline shift errors), 36.3% of targets had D95 and V95 values of <95%. Coverage worsened substantially when the baseline shift errors were increased to 1.0 mm. D95 and V95 values were >95% for about 77.3% of the targets. Only 11.4% of the D95 and V95 values were >95% when the baseline shift errors were increased to 2.0 mm. When the rotational error was increased to 1.5° and baseline shift errors increased to 1.0 mm, the D95 and V95 values were >95% in only 3 cases. Conclusions: The multivariate regression model analysis in this study showed that the coverage of the target decreased further with reduced target volume, increasing the baseline drift, the rotation error, and the distance to the target. [ABSTRACT FROM AUTHOR]

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Objectives: Single-isocentre volumetric-modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance for patients with multiple liver metastases (MLM). However, the potential increase in dose spillage to normal liver tissue using a singleisocentre technique has not yet been studied. We comprehensively evaluated the quality of single- and multi-isocentre VMAT-SBRT for MLM and propose a RapidPlan-based automatic planning (AP) approach for MLM SBRT. Methods: A total of 30 patients with MLM (two or three lesions) were selected for this retrospective study. We manually replanned all patients treated with MLM SBRT by using the single-isocentre (MUS) and multi-isocentre (MUM) techniques. Then, we randomly selected 20 MUS and MUM plans for training to generate the single-isocentre RapidPlan model (RPS) and the multi-isocentre RapidPlan model (RPM). Finally, we used data from the remaining 10 patients to validate RPS and RPM. Results: Compared with MUS, MUM reduced the mean dose delivered to the right kidney by 0.3 Gy. The mean liver dose (MLD) was 2.3 Gy higher for MUS compared with MUM. However, the monitor units, delivery time, and V20Gy of normal liver (liver-gross tumour volume) for MUM were significantly higher than for MUS. Based on validation, RPS and RPM slightly improved the MLD, V20Gy, normal tissue complications, and dose sparing to the right and left kidneys and spinal cord compared with manual plans (MUS vs RPS and MUM vs RPM), but RPS and RPM significantly increased monitor units and delivery time. Conclusions: The single-isocentre VMAT-SBRT approach could be used for MLM to reduce treatment time and patient comfort at the cost of a small increase in the MLD. Compared with the manual plans, RapidPlan-based plans, especially RPS, have slightly improved quality. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a globally prevalent and deadly malignancy often diagnosed at advanced stages, which can be accompanied by liver metastases. Conventional chemotherapy is contraindicated in patients with severe liver failure because several chemotherapeutic agents are metabolized by the liver. The present study reports on the successful use of nivolumab in a patient with advanced GC and severe liver failure owing to multiple liver metastases. A 57-year-old man was admitted to Shimane Prefectural Central Hospital (Izumo, Japan) with a 2-week history of appetite loss and jaundice. An upper gastrointestinal endoscopy revealed advanced GC (type IV). Computed tomography examination confirmed wall thickening of the gastric pylorus and the presence of multiple liver metastases. A gastric mucosal biopsy confirmed the diagnosis of HER2-positive gastric adenocarcinoma. S-1 + cisplatin chemotherapy was initiated but had to be halted due to the rapid deterioration in liver function, ultimately leading to acute liver failure. The patient was discharged from the hospital under palliative care. The patient was referred to Shimane University Hospital (Izumo, Japan) for a second consultation. Upon admission, the patient presented with severe liver failure, a Child-Pugh score of 10 (Class C), elevated total bilirubin levels of 13.9 mg/dl (normal range: <1.8 mg/dl) and elevated CEA and CA19-9. Nivolumab treatment was initiated, and notably, there was a substantial reduction in bilirubin levels, an improvement in liver function after a single cycle and a partial response observed in imaging studies. Despite the initial poor prognosis, the patient achieved long-term survival, ultimately succumbing to the illness 2 years and 6 months following the initiation of treatment. The present case underscores the potential of immune checkpoint inhibitors, such as nivolumab, in the treatment of patients with cancer and severe liver failure. It also challenges the conventional constraints of chemotherapy, offering a promising direction for future research in this area. [ABSTRACT FROM AUTHOR]

Abstract Background Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo‐refractory multiple liver metastases. Methods Forty‐five patients with chemo‐refractory multiple (3‐10) liver metastases after standard systemic chemotherapy entered the single‐institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3, respectively. The median of V15Gy, V30Gy, and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively. Results Forty‐two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1‐year survival rate was 29%. The median local control (LC) period was 5 months and the 6‐month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation‐induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil‐to‐lymphocyte ratio (NLR), and low pretreatment monocyte‐to‐lymphocyte ratio (MLR) were associated with poorer prognoses. Conclusions Helical tomotherapy for chemo‐refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first‐line treatment in combination with systemic chemotherapy should be considered. Trial registration number CROG 12005.

Background: Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo‐refractory multiple liver metastases. Methods: Forty‐five patients with chemo‐refractory multiple (3‐10) liver metastases after standard systemic chemotherapy entered the single‐institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3, respectively. The median of V15Gy, V30Gy, and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively. Results: Forty‐two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1‐year survival rate was 29%. The median local control (LC) period was 5 months and the 6‐month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation‐induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil‐to‐lymphocyte ratio (NLR), and low pretreatment monocyte‐to‐lymphocyte ratio (MLR) were associated with poorer prognoses. Conclusions: Helical tomotherapy for chemo‐refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first‐line treatment in combination with systemic chemotherapy should be considered. Trial registration number: CROG 12005. [ABSTRACT FROM AUTHOR]

Abstract Background Gastric cancer with multiple liver metastases have poor prognosis. Recently, stage IV gastric cancer patients who respond well to systemic chemotherapy can be treated by gastrectomy. We herein report a case of advanced gastric cancer with liver metastases who was successfully downstaged by systemic chemotherapy and underwent conversion surgery. Case presentation A 60-year-old male patient was diagnosed with gastric cancer with multiple liver metastases [cT3N3M1, stage IV]. After 18 courses of S-1 plus cisplatin combination chemotherapy (S-1 administered orally (80 mg/m2/day) twice a day for 21 consecutive days and cisplatin (60 mg/m2) infused on day 8), marked regression of liver metastasis was achieved, and we performed open total gastrectomy with D2 lymph node dissection. The patient was discharged from the hospital 10 days after the operation. Histopathological examination revealed no malignant cells in the lymph nodes [ypT1bN0M0, stage IA]. S-1 as the adjuvant chemotherapy was administered for 12 months, and the patient is alive without a recurrence for 33 months after surgery. Conclusions Conversion surgery may improve the poor prognosis of gastric cancer.

We report a 52‐year‐old woman with inoperable malignant insulinoma with multiple liver metastases. Histological examination of biopsy specimens from the pancreatic and hepatic lesions revealed pancreatic neuroendocrine tumor (pNET), G2. The tumor cells were positive for somatostatin receptor (SSTR) 2, 5, and the mammalian target of rapamycin (mTOR). Monthly intramuscular administration of octreotide LAR and once‐daily oral administration of everolimus combination treatment markedly reduced the sizes of liver metastases, and hypoglycemia was well controlled. Combination treatment with somatostatin analog and mTOR inhibitor may be another effective approach in inoperable metastatic malignant insulinoma. [ABSTRACT FROM AUTHOR]

The prognosis of pancreatic cancer is one of the worst of all cancers. Though the routine use of modern targeted and immunotherapy is still pending, the recently applied new chemotherapy combinations resulted in obvious improvement in the clinical management of pancreatic cancer. Adjuvant treatment followed by radical operation can increase the survival of the patients, moreover, neoadjuvant therapy for locally advanced tumors is associated with higher resectability rate. However, in metastatic disease only palliative chemotherapy could be indicated due to the dismal prognosis. The introduction of new chemotherapy combinations produced a major evolution by extending the median survival time of these patients. According to recent publications, even complete remission of the metastases can be achieved by the palliative chemotherapy, justifying a radical operation. This approach can be more advantageous, compared to patients treated with chemotherapy only. Reporting our two primary metastatic cases, we also endorse this new approach. The clinical significance of complex management is justified in the case of oligopersistence which is traditionally treated only with palliative systemic therapy. Orv Hetil. 2023; 164(43): 1712-1718.

Background: Gastric cancer with multiple liver metastases have poor prognosis. Recently, stage IV gastric cancer patients who respond well to systemic chemotherapy can be treated by gastrectomy. We herein report a case of advanced gastric cancer with liver metastases who was successfully downstaged by systemic chemotherapy and underwent conversion surgery. Case presentation: A 60-year-old male patient was diagnosed with gastric cancer with multiple liver metastases [cT3N3M1, stage IV]. After 18 courses of S-1 plus cisplatin combination chemotherapy (S-1 administered orally (80 mg/m/day) twice a day for 21 consecutive days and cisplatin (60 mg/m) infused on day 8), marked regression of liver metastasis was achieved, and we performed open total gastrectomy with D2 lymph node dissection. The patient was discharged from the hospital 10 days after the operation. Histopathological examination revealed no malignant cells in the lymph nodes [ypT1bN0M0, stage IA]. S-1 as the adjuvant chemotherapy was administered for 12 months, and the patient is alive without a recurrence for 33 months after surgery. Conclusions: Conversion surgery may improve the poor prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Objectives: Single-isocentre volumetric-modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance for patients with multiple liver metastases (MLM). However, the potential increase in dose spillage to normal liver tissue using a single-isocentre technique has not yet been studied. We comprehensively evaluated the quality of single- and multi-isocentre VMAT-SBRT for MLM and propose a RapidPlan-based automatic planning (AP) approach for MLM SBRT., Methods: A total of 30 patients with MLM (two or three lesions) were selected for this retrospective study. We manually replanned all patients treated with MLM SBRT by using the single-isocentre (MUS) and multi-isocentre (MUM) techniques. Then, we randomly selected 20 MUS and MUM plans for training to generate the single-isocentre RapidPlan model (RPS) and the multi-isocentre RapidPlan model (RPM). Finally, we used data from the remaining 10 patients to validate RPS and RPM., Results: Compared with MUS, MUM reduced the mean dose delivered to the right kidney by 0.3 Gy. The mean liver dose (MLD) was 2.3 Gy higher for MUS compared with MUM. However, the monitor units, delivery time, and V20Gy of normal liver (liver-gross tumour volume) for MUM were significantly higher than for MUS. Based on validation, RPS and RPM slightly improved the MLD, V20Gy, normal tissue complications, and dose sparing to the right and left kidneys and spinal cord compared with manual plans (MUS vs RPS and MUM vs RPM), but RPS and RPM significantly increased monitor units and delivery time., Conclusions: The single-isocentre VMAT-SBRT approach could be used for MLM to reduce treatment time and patient comfort at the cost of a small increase in the MLD. Compared with the manual plans, RapidPlan-based plans, especially RPS, have slightly improved quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Gong, Liu, Guo, Dai, Yuan, Wang and Zhang.)

This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy. [ABSTRACT FROM AUTHOR]

A 32-year-old woman underwent modified radical mastectomy for right breast cancer (invasive ductal carcinoma, f, INF β, v0, ly1, pT2, pN1, M0, Stage IIB ER (±), PR (-), Her2 (3+)) in June 2003, and received postoperative systemic adjunctive chemotherapy using epirubicin combined with cyclophosphamide, followed by paclitaxel. In August 2004, after a disease-free interval of 14 months, liver metastasis appeared, and therefore from September 2004, combination chemotherapy with oral capecitabine (2,400 mg/day) and injected trastuzumab (120 mg/week) was started. After 3 cycles, all the metastases responded and this marked response has been maintained for 16 months. This therapy is currently being continued (19 cycles), and no serious side effects have been encountered. Capesitabine and trastuzumab combination therapy is effective for recurrent breast cancer showing overexpression of HER2 and resistance to taxane, and can be considered as a first-line therapy for this purpose. It is anticipated that many cases treated with this regimen will be reported and discussed in the near future. [ABSTRACT FROM AUTHOR]

We report a 72-year-old man who was diagnosed by gastroscopy as having a type III poorly differentiated adenocarcinoma in the lesser curvature, with the longest diameter being 10 cm. An abdominal computed tomography (CT) scan revealed multiple liver metastases, thickening of the gastric wall, and an enlarged paraaortic lymph node. The serum carcinoembryonic antigen (CEA) level was 60 ng/ml and the carbohydrate antigen (CA) 19–9 level was 1355 U/ml. The patient received combined chemotherapy with doxifluridine (800 mg/body per day) and paclitaxel (one course comprised three weekly infusions at a dose of 70 mg/m2 followed by 1-week rest). After the completion of three courses, the patient achieved a complete response (CR), with complete disappearance of the primary tumor, the metastatic foci in the liver, and the enlarged abdominal lymph nodes; as well, the tumor markers were normalized. Adverse effects included only mild anorexia that was limited to grade 1. He maintained a CR for 1 year and 2 months. Combination chemotherapy with paclitaxel and doxifluridine can be an effective treatment for unresectable advanced gastric carcinoma. [ABSTRACT FROM AUTHOR]

The somatostatin analogue octreotide was effective in controlling systemic effects related to multiple liver metastases from a gastrinoma. A 61-year-old man underwent distal gastrectomy for gastrinoma in the duodenum, because a curative resection was not feasible due to metastases found in paraaortic lymph nodes during operation. Multiple liver metastases, associated with an increase in serum gastrin concentration, were found by magnetic resonance imaging 16 months after the operation. Although chemotherapy with dimethyltrizenoimidazole carboxamide was not effective, subcutaneous administration of octreotide was effective in controlling the growth of the liver metastases and in stabilizing serum gastrin. The patient now receives subcutaneous injections of octreotide, at 200µg a day, twice a week, as an outpatient. [ABSTRACT FROM AUTHOR]

The Japanese guideline for gastroenteropancreatic neuroendocrine tumor treatment recommends everolimus or sunitinib as first-line treatment for unresectable pancreatic neuroendocrine tumors (PNETs). Streptozocin (STZ) is recommended as an alternative. We encountered a patient with PNET who had multiple liver metastases and who showed a remarkable response to third-line STZ. The patient was a 50-year-old man with a pancreatic head tumor 32 mm in diameter. We planned to perform subtotal stomach-preserving pancreaticoduodenectomy, but abandoned resecting the pancreas during the surgery upon discovering a small liver tumor 3 mm in diameter, examination of frozen sections of which revealed a poorly differentiated adenocarcinoma. However, the final pathological examination revealed that the liver nodule was a PNET; hence, we completed the subtotal stomach-preserving pancreaticoduodenectomy 5 weeks after the first laparotomy. The patient received no adjuvant chemotherapy after surgery. Twenty-one months later, we discovered 20 scattered liver metastases via computed tomography; these were considered unresectable. Therefore, we administered everolimus for 7 months, but the patient developed interstitial pneumonia and experienced metastatic progression. Subsequent sunitinib administration for 6 months was ineffective. Finally, we chose STZ (1000 mg/m 2 , weekly) as a third-line treatment, which produced a partial response for 10 months. The patient remains alive 38 months after the detection of recurrence. As the order in which anti-cancer drugs should be administered to treat PNET has not been determined, additional predictors of their therapeutic efficacy should be investigated., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© The Japan Society of Clinical Oncology 2019.)

Background and Objectives: The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM., Methods: Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan., Results: There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023)., Conclusions: The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)