Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

Tey, Jeremy; Choo, Bok Ai; Leong, Cheng Nang; Loy, En Yun; Wong, Leong Sing; Lim, Keith; Lu, Jiade J.; Koh, Winston T. H.

doi:10.1097/md.0000000000000118

Cited by 66 publications

(68 citation statements)

References 12 publications

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“…Despite advancements in the early detection and treatment of gastric cancer, the prognosis from curative treatment remains poor, and more than 50% of the patients will develop metastatic disease [ 3 – 5 ]. Local symptoms that occur frequently are pain, gastric outlet obstruction, especially tumor bleeding from gastric lesions such as hematemesis, melena, and repeated anemia [ 6 – 9 ]. For such patients, physicians may consider several treatment options, such as endoscopic intervention, palliative gastrectomy or surgical bypass, palliative chemotherapy, or radiotherapy (RT) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Palliative external beam radiotherapy for the treatment of tumor bleeding in inoperable advanced gastric cancer

Lee

Jang

2017

BMC Cancer

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BackgroundTo assess the outcomes and prognostic factors associated with palliative external beam radiotherapy (EBRT), administered to patients with advanced gastric cancer.MethodsForty-two patients with bleeding gastric tumors that received EBRT for palliation were analyzed. The response to EBRT was assessed by the palliation of tumor bleeding. Patients were classified as either responders, or non-responders to EBRT. The prognostic utility of clinical and dosimetric variables was examined in a multivariate logistic regression model. The optimal dose cutoff to classify the two groups was determined with receiver operating characteristic analysis.ResultsThe palliation of gastric tumor bleeding after EBRT was achieved in 29 patients (69.0%). The time to resolve tumor bleeding ranged from 1 to 84 days (median, 15 days). The median duration of palliation was 14.9 weeks. The median EBRT dose was 40 Gy in responders vs. 21 Gy in non-responders, with the difference being significant (p < 0.001). The biologically effective dose (using α/β = 10, BED10) for responders was significantly higher than the BED10 for non-responders (median 48 Gy vs. 26.4 Gy, p < 0.001), and the optimal cut off value to separate the two groups was 36 Gy (p < 0.001). The absence of distant metastasis and the use of concurrent chemotherapy generally showed a better EBRT response (p = 0.079 and p = 0.079, respectively). In the multivariate analysis, BED10 ≥ 36 Gy was the most significant factor associated with EBRT response (p = 0.001). Overall survival (OS) and re-bleeding-free survival was median 12.6 weeks and 14.9 weeks. The responders to EBRT showed superior OS (16.6 vs. 5.1 months, p < 0.001). Neither acute nor chronic toxicities of grade 3 or higher were observed.ConclusionsEBRT is an effective method for treating tumor bleeding in advanced gastric cancer, and does not induce severe toxicity.

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Section: Introductionmentioning

confidence: 99%

Palliative external beam radiotherapy for the treatment of tumor bleeding in inoperable advanced gastric cancer

Lee

Jang

2017

BMC Cancer

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“…However, while there may be no difference between low and high BED regimens in symptom palliation, local control may be improved with higher BED regimens. One study showed a trend for poorer local control with low BED regimens of ≤39 Gy compared with higher BED regimens . Similarly, Kim et al from MD Anderson also suggested that low BED regimens of <41 Gy predicted for poorer local control compared to higher BED regimens …”

Section: Discussionmentioning

confidence: 98%

“…Different treatments have been employed to treat symptoms from local tumor extension. These include argon plasma laser coagulation, palliative gastrectomy, gastric bypass, stenting, palliative chemotherapy and palliative radiotherapy (RT) . Palliative RT is attractive as it is non‐invasive and has been shown to be effective in randomized trials in palliating bleeding and obstructive symptoms in patients with advanced lung and bladder cancers …”

Section: Introductionmentioning

confidence: 99%

Palliative radiotherapy in symptomatic locally advanced gastric cancer: A phase II trial

Tey

Zheng²,

Soon

et al. 2019

Cancer Medicine

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To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10‐point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ‐C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ‐C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients.

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“…Gastric cancer is a malignant disease of the digestive system; it has a high incidence rate and is the second leading cause of cancer-associated mortality worldwide (1). The clinical symptoms in the early stage are not obvious, and predominantly include upper abdominal pain, heartburn, nausea and loss of appetite (2,3). Currently, radical gastrectomy is the predominant treatment method for patients with early stage disease.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting the role of Skp2 suppresses cell proliferation and tumorigenesis of human gastric cancer cells via the upregulation of p27kip1

Wen

Wang

Yang

2016

Molecular Medicine Reports

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Gastric cancer is a malignant disease of the digestive system with high rates of incidence and mortality. S‑phase kinase‑associated protein 2 (Skp2) is a novel oncogene, which has been identified to be important in tumor progression and metastasis. In order to clarify the role of Skp2 in human gastric cancer, the present study detected the expression of Skp2 in human gastric cancer tissues, and investigated the molecular mechanism of Skp2 in the progression of gastric carcinoma. The results of the initial bioinformatics analysis showed that Skp2 was significantly upregulated in 31 specimens of primary gastric cancer from a UK patient cohort, and in 10 gastric cancer lines of a side population, compared with normal gastric tissues (P<0.01). Specimens from 47 patients with gastric cancer and 19 normal gastric tissue specimens were obtained and analyzed using western blot analysis. The positive rate of expression of Skp2 was 87.2%, indicating that the expression of Skp2 was observed in 41 specimens of the detected gastric cancer samples, whereas the positive rate of the expression of Skp2 was 5.6% in the normal gastric samples (P<0.01). In the human gastric cancer cell lines, the defective regulation of Skp2 or presence of an Skp2 inhibitor inhibited the proliferation of BGC‑823 and MKN‑45 cells. In addition, the Skp2 inhibitor suppressed the proliferation of gastric cancer cells in a time‑ and dose‑dependent manner. Furthermore, transfection with Skp2 short hairpin (sh)RNA or treatment with SKP inhibitor C1 for 48 and 72 h led to the accumulation of p27kip1 in Hela cells. Tumorigenicity experiments involving nude mice showed that interference of the expression of Skp2 inhibited the growth of the human gastric tumor cells in the nude mice, and the tumor weights and volumes in the Skp2 shRNA group were significantly lower, compared with those in the negative control shRNA group (P<0.01) and untreated group (P<0.01). Taken together, these data suggested that Skp2 acted as an oncogene in human gastric cancer, and that Skp2‑mediated p27kip1 degradation contributed to the progression of gastric cancer. Abrogating the effects of Skp2 may effectively inhibit the growth of gastric cancer cells, which may be useful as a novel target in the clinical treatment of gastric cancer.

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Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

Cited by 66 publications

References 12 publications

Palliative external beam radiotherapy for the treatment of tumor bleeding in inoperable advanced gastric cancer

Palliative external beam radiotherapy for the treatment of tumor bleeding in inoperable advanced gastric cancer

Palliative radiotherapy in symptomatic locally advanced gastric cancer: A phase II trial

Inhibiting the role of Skp2 suppresses cell proliferation and tumorigenesis of human gastric cancer cells via the upregulation of p27kip1

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