The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Application of project-based learning in clinical teaching of radiation physics for radiotherapy residents / 中华放射肿瘤学杂志

Objective:To observe the effect of project-based learning (PBL) in the clinical teaching of radiation physics.Methods:Thirty-two residents specializing in radiotherapy were included in the study. In the experimental group ( n=16), PBL was adopted, while traditional clinical teaching method was employed in the control group ( n=16). After the rotation, the assessment was conducted, as well as a questionnaire survey was performed, including five aspects: overall satisfaction, understanding of radiation physics knowledge, learning motivation, learning burden, and learning efficiency. Results:The assessment score in the experimental group was 86.31±5.41, which was higher than 75.28±5.91 in the control group, and the difference was statistically significant. Residents in the experimental group were satisfied with the effect of PBL.Conclusion:Compared with the traditional teaching method, PBL can improve the learning motivation, efficiency, and performance of radiotherapy residents, which is highly recognized by the residents.

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Oral contrast agents lead to underestimation of dose calculation in volumetric-modulated arc therapy planning for pelvic irradiation / 中华医学杂志(英文版)

BACKGROUND@#The effects of oral contrast agents (OCAs) on dosimetry have not been studied in detail. Therefore, this study aimed to examine the influence of OCAs on dose calculation in volumetric-modulated arc therapy plans for rectal cancer.@*METHODS@#From 2008 to 2016, computed tomography (CT) images were obtained from 33 rectal cancer patients administered OCA with or without intravenous contrast agent (ICA) and 14 patients who received no contrast agent. CT numbers of organs at risk were recorded and converted to electronic densities. Volumetric-modulated arc therapy plans were designed before and after the original densities were replaced with non-enhanced densities. Doses to the planned target volume (PTV) and organs at risk were compared between the plans.@*RESULTS@#OCA significantly increased the mean and maximum densities of the bowels, while the effects of ICA on these parameters depended on the blood supply of the organs. With OCA, the actual doses for PTV were significantly higher than planned and doses to the bowel increased significantly although moderately. However, the increase in the volume receiving a high-range doses was substantial (the absolute change of intestine volume receiving ≥52 Gy: 1.46 [0.05-3.99, cubic centimeter range: -6.74 to 128.12], the absolute change of colon volume receiving ≥50 Gy: 0.34 [0.01-1.53 cc, range: -0.08 to 3.80 cc]. Dose changes due to ICA were insignificant. Pearson correlation showed that dose changes were significantly correlated with a high intestinal volume within or near the PTV (ρ > 0.5, P  0.3, P < 0.05).@*CONCLUSIONS@#Contrast agents applied in simulation cause underestimation of doses in actual treatment. The overdose due to ICA was slight, while that due to OCA was moderate. The bowel volume receiving ≥50Gy was dramatically increased when OCA within the bowel was absent. Physicians should be aware of these issues if the original plan is barely within clinical tolerance or if a considerable volume of enhanced intestine is within or near the PTV.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study / 中华医学杂志(英文版)

Background@#Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT.@*Methods@#From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups.@*Results@#After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar–cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim).@*Conclusions@#Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study / 中华医学杂志(英文版)

BACKGROUND@#Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT.@*METHODS@#From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups.@*RESULTS@#After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim).@*CONCLUSIONS@#Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Comparison of dose-dense ABVD and standard ABVD in the treatment of early unfavorable and advanced Hodgkin's lymphoma: a retrospective analysis / 华中科技大学学报（医学）（英德文版）

This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with the dose-dense ABVD regimen (ABVD-21) in terms of efficacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin's lymphoma (HL) according to German Hodgkin Study Group criteria from March 1999 to February 2011 were analyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates after completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival (PFS) and overall survival (OS) rates (84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD). Subgroup analyses showed that ABVD-21 was significantly better than ABVD for patients with IPS≥3 in terms of PFS and OS rates. Grade 3 to 4 leukopenia (51.8% vs. 28.8%, P=0.001) and neutropenia (57.6% vs. 39.0%, P=0.009) were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor control and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS≥3, may benefit from dose-dense ABVD.

Comparison of dose-dense ABVD and standard ABVD in the treatment of early unfavorable and advanced Hodgkin's lymphoma: a retrospective analysis / 华中科技大学学报（医学）（英德文版）

This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with the dose-dense ABVD regimen (ABVD-21) in terms of efficacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin's lymphoma (HL) according to German Hodgkin Study Group criteria from March 1999 to February 2011 were analyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates after completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival (PFS) and overall survival (OS) rates (84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD). Subgroup analyses showed that ABVD-21 was significantly better than ABVD for patients with IPS≥3 in terms of PFS and OS rates. Grade 3 to 4 leukopenia (51.8% vs. 28.8%, P=0.001) and neutropenia (57.6% vs. 39.0%, P=0.009) were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor control and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS≥3, may benefit from dose-dense ABVD.

Impact of CCND1 A870G polymorphism on acute adverse events in postoperative rectal cancer patients treated with adjuvant concurrent chemoradiotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).</p><p><b>METHODS</b>Four hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model.</p><p><b>RESULTS</b>A total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea.</p><p><b>CONCLUSIONS</b>The genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.</p>

Fractionated stereotactic radiotherapy with vagina carotica protection technique for local residual nasopharyngeal carcinoma after primary radiotherapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Local failure of nasopharyngeal carcinoma (NPC) after radiotherapy (RT) remains one of the major treatment failures. This study aimed to evaluate the clinical efficacy and complications of fractionated stereotactic radiotherapy (FSRT) with vagina carotica protection technique for local residual of NPC patients after the primary RT.</p><p><b>METHODS</b>From August 2006 to August 2010, FSRT with vagina carotica protection technique was applied to 36 patients in our department, the patients aged between 13 and 76 years with a median of 41.3 years, 25 of them were male and 11 were female. According to 2002 Union for International Cancer Control (UICC) Staging System, the stages before primary radiotherapy were: IIa 2, IIb 5, III 18, IVa 7, IVb 4. In the first course of radiotherapy, 9 patients received conventional RT, 27 patients received intensity modulated radiotherapy (IMRT) and 20 out of the 36 patients received concurrent chemoradiotherapy. The total dose in the first course of RT was 69.96 - 76.90 Gy (median, 72.58 Gy). The intervals between the primary RT and FSRT ranged from 12 to 147 days (median, 39.8 days). Target volumes ranged from 1.46 to 32.98 cm(3) (median, 14.94 cm(3)). The total FSRT doses were 10.0 - 24.0 Gy (median, 16.5 Gy) with 2.0 - 5.0 Gy per fraction. The most common regimen was 15 Gy in 5 fractions of 3 Gy, the irradiation dose to vagina carotica was less than 2 Gy per fraction.</p><p><b>RESULTS</b>The median follow-up time was 34 months (range, 12 - 59 months). The 3-year local control rate was 100%; the 3-year overall survival rate was 94.4%; the 3-year disease-free survival rate was 77.8%. In this study, we had one case of cranial nerve injury, two cases of temporal lobe necrosis, and no nasopharyngeal massive hemorrhage was observed.</p><p><b>CONCLUSION</b>FSRT with vagina carotica protection technique is an effective and safe RT regimen for local residual of NPC with reduction of radiation-related neurovascular lesions.</p>

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma / 癌症

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Stereotactic body radiation therapy favors long-term overall survival in patients with lung metastases: five-year experience of a single-institution / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Metastatic lung cancer is one of the most common oncologic problems. This study aimed to evaluate the long-term clinical outcome of stereotactic body radiation therapy (SBRT) for metastatic lung tumors.</p><p><b>METHODS</b>We retrospectively reviewed the 71 patients with lung metastases, who had 172 lesions treated with SBRT from January 2000 to December 2006. All patients were unfit or failed after surgery and/or chemotherapy. The median total dose was 48 Gy (range, 30 - 60) in 4 (range, 2 - 12) fractions. The median size of the irradiated lesions was 2.1 cm (range, 0.9 - 7.9 cm).</p><p><b>RESULTS</b>All but two patients received follow up. The median follow-up time was 24.7 months (range, 2.9 - 114.4 months). The median follow-up time for living patients was 86.8 months (range, 58.1 - 114.4 months). The 1-, 3-, 5-year local control and overall survival rates were 88.8%, 75.4%, 75.4% and 78.9%, 40.8%, 25.2%. Multivariate analysis showed that the absence of extrapulmonary metastases (P = 0.024; hazard ratio (HR), 1.894; 95% confidence interval (CI), 1.086 - 3.303) and disease-free interval ≤ 12 months (P = 0.014; HR, 0.511; 95%CI, 0.299 - 0.873) were independent prognostic factors. No grade 3 or more acute and late toxicities occurred. Only one patient developed a non-symptomatic rib fracture.</p><p><b>CONCLUSION</b>SBRT could be an alternative treatment to surgery for subsets of patients with lung metastases with favorable long-term survival and tolerable complications.</p>

Prognostic value of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in node positive breast cancer patients treated by mastectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy.</p><p><b>METHODS</b>The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).</p><p><b>RESULTS</b>141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS.</p><p><b>CONCLUSION</b>ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.</p>

Postmastectomy radiotherapy in moderate-and high-risk elderly breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the role of postmastectomy radiotherapy (PMRT) in moderate- and high-risk elderly breast cancer patients.</p><p><b>METHODS</b>The clinicopathological data of 874 breast cancer patients treated with mastectomy and axillary dissection were retrospectively analyzed. The T1-2N1 patients were defined as moderate- risk (IR) group, and T3-4 and/or N2-3 cases as high-risk (HR) group. The locoregional recurrence (LRR) and overall survival (OS) rates were calculated and compared according to different age groups and radiotherapy status. Kaplan-Meier method and Log-rank test was used for calculation and comparison of the survival curves of different patient groups.</p><p><b>RESULTS</b>The median follow up time was 47 months. 108 (12.4%) patients were > or = 65 years. For patients who were < 65 and > or = 65 years, 18.1% and 15.3% received PMRT in the IR group, and 82.7% and 52.2% received PMRT in the HR group, respectively. For patients > or = 65 years, the 5-year LRR rates were 0% and 14.2% (P = 0.242) and 5-year OS rates were 100% and 75.2% (P = 0.159) for the PMRT-IR and non-PMRT-IR groups, respectively. The 5-year LRR rates were 0% and 14.1% (P = 0.061), 5-year OS rates were 84.6% and 77.4% (P = 0.597) for the PMRT-HR and non-PMRT-HR groups, respectively. For patients < 65 years, the 5-year LRR rates were 0% and 9.9% (P = 0.035) and 5-year OS rates were 87.0% and 82.1% (P = 0.739) for the PMRT-IR and non-PMRT-groups, respectively. The 5-year LRR rates were 7.2% and 26.1% (P = 0.000), 5-year OS rates were 79.2% and 57.7% (P = 0.000) for the PMRT-HR and non-PMRT-HR groups, respectively.</p><p><b>CONCLUSION</b>With the increasing of age, there is a trend of decreasing use of postmastectomy radiotherapy in high-risk breast cancer patients. Postmastectomy radiotherapy can improve the locoregional control for high-risk patients and maybe considered even for those who are > or = 65 years.</p>

Comparison of treatment planning by carbon ion radiotherapy and by intensity-modulated radiotherapy for prostatic adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the potential benefit of carbon ion radiotherapy (C-ion RT) through comparison with photon intensity-modulated radiotherapy (IMRT) in dose distribution for prostatic adenocarcinoma.</p><p><b>METHODS</b>In randomly selected 5 patients, treatment planning of C-ion RT (4 coplanar beams) and IMRT (7 coplanar fields) were worked out by computer working station. In order to make a meaningful comparison, it was defined that the 95% isodose surface had to cover 100% of the PTV in each plan; all dose was given as normalized dose with the definition of the minimum dose of the PTV being equal to 95% of prescribed dose. Dose-volume histograms (DVHs) of the tumor and organ-at-risks (OARs) were calculated. Volume irradiated more than or equal to some specified doses, conformity index ( CI) , and inhomogeneity coefficient (IC) of each treatment plan was compared, respectively.</p><p><b>RESULTS</b>With C-ion RT, the mean irradiated volumes (in %) of the rectum were significantly smaller than that with IMRT except for 95% dose level, and C-ion RT could provide complete protection to the posterior rectal wall. In addition, C-ion RT could also remarkably reduce the dose to the bladder, femoral heads and non-target normal tissues at each dose level. Dose conformation and homogeneity in the target volume of C-ion RT were better than that in IMRT (mean CI50%, 3.36 vs. 5.04, mean CI95%, 1.20 vs. 1.46, mean IC, 0.03 vs. 0.12).</p><p><b>CONCLUSION</b>Compared with IMRT, C-ion RT can obtain better dose distribution, and may reduce tumor recurrence and radiation-induced complications in prostatic adenocarcinoma.</p>

Treatment option and outcome for patients with primary non-Hodgkin's lymphoma of the nasal cavity / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The optimal treatment for primary non-Hodgkin's lymphoma (NHL) of the nasal cavity remains controversial. This study was to analyze the initial response rate of radiotherapy and chemotherapy, and the influence of different treatment modalities on prognosis.</p><p><b>METHODS</b>From January 1996 to December 2002, the clinical data of 129 patients with previously untreated nasal NHL were retrospectively reviewed with all lesions confirmed by pathology. 116 patients were morphologically diagnosed as having nasal NK/T cell lymphoma. The immunophenotype was available in 57 cases and 52 (91.2%) of them were confirmed as NK/T-cell lymphoma. According to the Ann Arbor Staging System, 102 patients had stage I(E), 22 stage II(E), and 5 stage IV(E) disease. Among the 124 patients with stage I(E) and II(E) diseases, 22 patients received radiotherapy alone, 7 chemotherapy alone, and 95 combined modality therapy (CMT). Of these 95 patients treated with CMT, 45 patients were treated with radiotherapy followed by chemotherapy, and 50 with chemotherapy followed by radiotherapy. The primary treatment for stage IV(E) patients was chemotherapy with or without radiotherapy to the primary tumor.</p><p><b>RESULTS</b>The overall 5-year survival (OS) and disease free survival (DFS) for all patients was 68.0% and 55.8%, respectively. It was 71.7% and 60.9% for stage I(E), and 70.6% and 47.0% for stage II(E), respectively (P > 0.05). The OS and DFS at the 5th year were 83.1% and 68.0% for patients who achieved complete response (CR), and 18.0% and 15.5% for those who did not, respectively (P = 0.000). Of the 124 patients with stage I(E) and II(E) disease, 67 patients were treated with radiotherapy alone (22 patients) or radiotherapy followed by chemotherapy (45), whereas 57 were treated with chemotherapy followed by radiotherapy (50) or chemotherapy alone (7). The CR rate after radiotherapy was 74.7%, however, it was only 19.3% after chemotherapy (P = 0.000). Of the 46 patients with PR, SD or PD after chemotherapy, 42 still had locoreginally localized lesion and 31 of these patients achieved CR by following radiotherapy which revealed satisfactory results. For stage I(E) and II(E) disease, the 5-year OS and DFS were 76.0% and 65.0% for radiotherapy with or without chemotherapy, and 74.4% and 56.2% for chemotherapy followed by radiotherapy. The difference was statistically not significant. However, 7 stage I(E) and II(E) patients were treated with chemotherapy alone, and 4 of them died of disease progression, with 1-year survival of 26.7%.</p><p><b>CONCLUSION</b>The majority of Chinese patients with primary nasal NHL are NK/T cell in origin. The complete response rate by radiotherapy is much higher than that by chemotherapy. The addition of chemotherapy to radiotherapy did not improve the survival of patients with early stage nasal lymphoma. Radiotherapy is suggested as the primary treatment for stage I(E) and II(E) nasal NK/T cell lymphoma.</p>

Comparison of preliminary results of involved-field with extended field radiotherapy combined with chemotherapy for early stage Hodgkin's disease / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate whether involved-field (IF) radiotherapy is equally effective and less toxic in comparison with extended-field (EF) radiotherapy for patients with early-stage Hodgkin's disease (HD) who received combined modality therapy.</p><p><b>METHODS</b>The data of 88 early-stage HD patients treated with combined modality therapy were retrospectively reviewed. According to Ann Arbor classification, 12 patients (13.7%) had stage IA disease, 56 stage IIA (63.6%), and 20 IIB (22.7%). Forty-two (47.7%) patients underwent involved field radiotherapy (IF group), whereas the other 46 (52.3%) received extended field radiotherapy (EF group).</p><p><b>RESULTS</b>Of 6 patients who developed recurrence, 3 (7.1%) were in IF group and the other 3 (6.5%) in EF group. Only one patient's recurrence developed inside the radiation field in EF group. Three patients (7.2%) in IF group and 9 (19.5%) in EF group had WHO grade 1 and 2 leukopenia (P = 0.089). Overall survival rate at 1-, 2- and 3-year was 100.0%, 97.1%, and 97.1% in IF group versus 100.0%, 100%, and 95.8% in EF group (P = 0.86), respectively. Freedom from progression survival rate at 1-, 2- and 3-year was 97.6%, 94.8%, and 91.7% in IF group versus 97.8%, 93.2%, and 93.2% in EF group (P = 0.65), respectively.</p><p><b>CONCLUSION</b>Compared with extended-field radiotherapy, involved-field radiotherapy is equally effective and less toxic for patient with early-stage Hodgkin's disease treated with combined modality therapy.</p>

Prognostic factors and treatment outcome in early stage nasal NK/T cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze initial response rate of radiotherapy and chemotherapy for early nasal NK/T-cell lymphoma, and its prognostic factors.</p><p><b>METHODS</b>From January 1996 to December 2002, 116 patients with nasal NK/T-cell lymphoma were diagnosed pathologically. Immunophenotyping was performed in 50 cases. According to Ann Arbor staging classification, 95 patients were stage I(E) and 21 II(E). Of the 116 patients, 22 received radiotherapy alone, 6 chemotherapy alone and 88 combined modality therapy (CMT), including, 41 radiotherapy followed by chemotherapy, and 47 chemotherapy followed by radiotherapy.</p><p><b>RESULTS</b>The 5-year overall survival (OS) rate and disease free survival (DFS) rate for all patients was 74.1% and 61.5%, respectively. For stage I(E) and II(E) patients, the 5-year OS rate was 75.1% and 68% (P = 0.45), and DFS rate was 64.7% and 47.8%, respectively (P = 0.07). The 5 year OS rate and DFS rate were 86.5% and 71.5% for patients who achieved complete response (CR), and 18.4% and 17.2% for those who didn't, respectively (P = 0.000). Sixty-three patients were treated with radiotherapy alone or radiotherapy followed by chemotherapy, while 53 with chemotherapy followed by radiotherapy or chemotherapy alone. The CR rate for radiotherapy was 74.6% while for chemotherapy was 20.8% (P = 0.000). The 5-year OS rate and DFS rate were 76.8% and 65.4% for radiotherapy with or without chemotherapy, and 78.8% and 61.8% for chemotherapy followed by radiotherapy (P > 0.05). Multivariate analysis by COX regression showed that CR rate was the only independent prognostic factor.</p><p><b>CONCLUSION</b>The CR rate of radiotherapy is much higher than that of conventional chemotherapy. Addition of chemotherapy to radiotherapy do not improve the survival of patients with early stage nasal NK/T-cell lymphoma. Radiotherapy is the primary treatment for stage I and II nasal NK/T-cell lymphoma.</p>

Phase I study of postoperative concurrent chemoradiation with capecitabine as adjuvant treatment for stage II/III operable rectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This phase I study is to determine the maximal tolerated dose and the dose-limiting toxicity of capecitabine combined with standard radiotherapy (RT) as postoperative adjuvant treatment for rectal cancer patients.</p><p><b>METHODS</b>Stage II/III rectal cancer patients 18 - 75 years of age had undergone curative surgery with Karnofsky score > or = 70% were eligible to be included in this study. Total dose of RT DT 50 Gy was delivered to the pelvic area in fraction of 2.0 Gy per day for 5 weeks. Capecitabine was orally administered concurrently with radiotherapy for a total of 2 cycles in escalating doses: twice daily at 12 hour interval for consecutive 14 days as one cycle, separated by a seven day rest, then followed by another cycle. From March 2004 to May 2005, 24 patients were included and treated at the following dose levels: daily 1000 mg/m(2) (3 patients), 1200 mg/m(2) (3 patients), 1400 mg/m(2) (3 patients), 1500 mg/m(2) (3 patients), 1600 mg/m(2) (6 patients), and 1700 mg/m(2) (6 patients). Dose-limiting toxicities (DLT) including grade 3 or grade 4 hematologic and nonhematologic toxicity were observed.</p><p><b>RESULTS</b>Dose-limiting toxicity was observed in one patient treated at dose of 1600 mg/m(2) with grade 3 diarrhea, and in 2 patients at dose of 1700 mg/m(2) with one grade 3 and one grade 4 diarrhea.</p><p><b>CONCLUSION</b>Diarrhea is the most common dose-limiting toxicity. In our study, the maximal tolerated dose (MTD) of capecitabine given concurrently with radiotherapy was daily 1600 mg/m(2), from D1 to D14 separated by 7-day rest for 2 cycles. Capecitabine given concurrently with standard radiotherapy is safe and tolerable for operated stage II/III rectal cancer patients.</p>