Evaluation on genotoxicities of raceanisodamine hydrochloride injection / 药学实践杂志

Objective To study the genotoxicities of raceanisodamine hydrochloride injection. Methods Bacterial reverse mutation test, in vitro Chromosomal aberration test and in vivo Micronucleus test were performed to investigate the genotoxicities of raceanisodamine hydrochloride injection. Results The Ames test showed that raceanisodamine hydrochloride injection did not increase mutagenicity for TA1535, TA102, TA100, TA98 and TA97 strains at the dosage of 0.5, 5, 50, 500, 5000 μg per plate under two parallel system conditions (±S9). Results of CA test indicated that there was no statistical difference between raceanisodamine hydrochloride injection groups (doses of 58.75,117.5 and 235.0 μg/ml) and the solvent control group under two parallel system conditions (±S9). In MNT test, with doses of 7.5, 15.0 and 30.0 mg/kg respectively, the micronucleus induction rate of bone marrow of ICR mice was not statistically significant (P>0.05) when compared with that of vehicle control group in all dose groups. Conclusion Under the conditions of these study, the results indicated that raceanisodamine hydrochloride injection had no mutagenicity to Salmonella typhimurium, had no aberration effect on the chromosome of mammalian cultured cells, and had no effect on inducing micronucleus of bone marrow polychromatic erythrocytes in ICR mouse. All test results showed that raceanisodamine hydrochloride injection had no potential carcinogenicities and genetic toxicities under the test conditions.

Outcome of Concurrent Chemoradiation in Inoperable Muscle Invasive Urothelial Carcinoma of Urinary Bladder in terms of Locoregional Response and Toxicities — A Longitudinal Study in a Tertiary Care Hospital

Background : The presenting study was performed to assess the efficacy in terms of tumour response and toxicity profile of a curative intent organ preservation approach in Inoperable Non-metastatic Muscle-Invasive Urinary Bladder Carcinoma. Materials and Methods : Prospective Interventional Single-Arm, Single Center study with a duration of one and half year in which 47 patients with Muscle-invaded Bladder Cancer were treated with Radiotherapy with 64 Gy in 32# along with Concurrent Chemotherapy with three weekly injection Cisplatin in dose of 70 mg/m2. Response evaluation was done using both Clinical and Radiological means and categorized using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For adverse events measurement: NCI CTCAE (Common Terminology Criteria for Adverse Events, v4.1) and RTOG/EORTC Acute and Late Morbidity criteria was used. Results : Of the 47 patients who completed chemoradiation, complete treatment response was seen in 25 patients (53.2%), 17 patients (36.2%) had partial response on initial assessment and one patient had disease progression both in form of locoregional and distant (lung) metastasis. Stable disease found in (8.5%). Patients with residual disease were advised to undergo salvage treatment. Grade 3 Nephrotoxicity reported in one patient, Grade 2 Cystitis in 32 patients (68.1%), while Grade 2 Diarrhoea occurred in four patients (8.5%). Hematological toxicity attributable to Chemoradiotherapy included Grade 2, Grade 3 Neutropenia seen in 6.4% and 2.1% respectively and Grade 2 Anaemia in 4.3% patients. Conclusion : Concurrent Chemoradiotherapy is well-tolerated, effective and convenient curative treatment option for patients with Inoperable Non-metastatic Muscle Invasive Carcinoma of Urinary Bladder

Efficacy and safety of capecitabine and oxaliplatin (CAPOX) treatment in colorectal cancer: An observational study from a tertiary cancer center in South India

Background: 5-fluorouracil (5-FU) was the standard treatment care for colorectal cancer (CRC), however, its efficacy was limited due to safety concerns. Capecitabine and oxaliplatin (CAPOX) treatment was found equivalent to 5-FU in efficacy and preferred now due to easy management and convenience in administration. Hence, the present study aims to determine the efficacy and safety associated with CAPOX treatment in a real world non clinical setting. Methods: 145 treatment-naive and newly diagnosed CRC patients were recruited in the study. Each patient received oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000 mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. Results: In the adjuvant setting, the observed disease-free survival rate was 62% (n=34) in the colon and 67% (n=15) in the rectum cancer patients at 2 years. The observed overall survival rate in the colon and rectal cancer was 80% (n=44) and 83% (n=18) respectively at 2 years. In the palliative setting the observed progression-free survival rate was 28% (n=13) in the colon and 33% (n=7) in rectal cancer patients at 2 years. The observed OSR at 2 years was 64% (n=30) in the colon and 67% (n=14) in the rectal cancer patients. Thrombocytopenia (17, 11.7%) and diarrhea (8, 5.5%) were the most commonly observed grade 3/4 hematological and gastrointestinal toxicities. Hand-foot syndrome and peripheral neuropathy were the major contributors for dose reduction (14, 9.6%), treatment delay (8, 5.4%), and drug discontinuation (9, 6.1%) in the study cohort. Conclusion: CAPOX treatment was found to be effective but associated with several dose-limiting toxicities.

Avaliação do tratamento quimioterápico paliativo com o esquema LDE- paclitaxel em pacientes portadores de metástases ósseas por neoplasia maligna / Evaluation of palliative chemotherapy treatment with the LDEpaclitaxel regimen in patients with bone metastases from malignant neoplas

Introdução: Pacientes com câncer em estádios avançados e metástases ósseas frequentemente não apresentam condições clínicas para a realização de esquemas quimioterápicos convencionais subsequentes, restringindo as opções de tratamento. Anteriormente, demonstramos que nanopartículas artificiais lipídicas (LDE), semelhantes à lipoproteína de baixa densidade (LDL) rica em colesterol, são captadas por tecidos malignos, e quando associadas aos quimioterápicos, após injeção pela via endovenosa, reduz drasticamente a toxicidade do tratamento. Os objetivos deste presente estudo foram avaliar a resposta clínica ao tratamento quimioterápico com paclitaxel (PTX) associado à LDE; avaliar as toxicidades clínicas e laboratorial, e a capacidade da associação LDE-PTX em reduzir a dor oncológica relacionada às metástases ósseas em pacientes com carcinoma de mama, próstata e pulmão, previamente tratados e não elegíveis para tratamento quimioterápico convencional subsequente. Métodos: Dezoito pacientes (8 com câncer de mama, 5 de próstata e 5 de pulmão) com metástases ósseas foram incluídos. O tratamento consistiu no esquema LDE-PTX na dose convencional do PTX (175 mg/m2 de superfície corpórea de 3/3 semanas) e os pacientes foram avaliados por resposta clínica, redução da dor óssea, uso de medicamentos opióides, e ocorrência de fraturas ósseas patológicas. Resultados: No total, 104 ciclos de quimioterapia foram realizados, e nenhum paciente apresentou toxicidade clínica, laboratorial, assim como não houve fraturas patológicas. Dos 18 pacientes incluídos, 9 tiveram sobrevida livre de progressão de doença 6 meses. Houve em todos os pacientes redução da dor óssea, permitindo substituição da medicação opióide por analgésico não opióide. Conclusão: A melhora significativa na dor óssea sem que tenha ocorrido toxicidade do tratamento, e o tempo de não progressão de doença 6 meses na metade dos pacientes sugere que esses pacientes tenham se beneficiado consistentemente do tratamento com a LDE-PTX. Portanto, a LDE-PTX pode tornar- se uma opção terapêutica interessante em pacientes com carcinomas de próstata, mama ou pulmão em estágios avançados e sem condições clínicas de se submeterem a outros esquemas quimioterápicos convencionais

Introduction: Patients with advanced cancer and bone metastases usually do not have clinical conditions to perform additional conventional chemotherapy regimens, restricting treatment options. Previously, we showed that lipid core nanoparticles (LDE), similar to cholesterol-rich low-density lipoprotein (LDL), are taken up by malignant tissues, and when associated to chemotherapy, after endovenous injection, it drastically decreases the toxicity of the treatment. The objectives of this study were to evaluate the clinical response to chemotherapy treatment with paclitaxel (PTX) associated with LDE; to evaluate the clinical and laboratorial toxicities, and the ability of the LDE-PTX to reduce cancer pain related to bone metastases in patients with breast, prostate or lung carcinoma, previously treated and not eligible for subsequent conventional chemotherapy treatment. Methods: Eighteen patients (8 with breast cancer, 5 with prostate and 5 with lung) with bone metastases were included. Treatment consisted of the LDE-PTX regimen at a conventional dose of PTX (175 mg/m2 body surface area, 3/3 weeks) and patients were evaluated for clinical response, reduction in bone pain, use of opioid medications, and the occurrence of pathological bone fractures. Results: In total, 104 chemotherapy cycles were performed, and none of the patients showed clinical or laboratorial toxicities, as well as there were no pathological fractures. Of the 18 patients evaluated, 9 had progression-fee survival 6 months. Patients had decrease in bone pain allowing replacement of opioid medication by another non-opioid analgesic. Conclusion: Significant improvement in bone pain without treatment toxicity, and time to disease progression of 6 months in half of the patients suggest that these patients have consistently benefited with LDE-PTX treatment. Therefore, LDE-PTX may become an interesting therapeutic option in patients with advanced stage of prostate, breast or lung carcinomas and without clinical conditions to undergo other conventional chemotherapy regimens

Nivolumab-associated pulmonary toxicities： a retrospective study based on FARES database from 2016 to 2019 / 上海预防医学

Objective:Nivolumab is one of the most common programmed death 1 （PD-1） inhibitors used as an immune checkpoint inhibitor （ICI）. It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration （FDA） Adverse Event Reporting System （FAERS） database from January 1， 2016 to September 30， 2019. Two types of disproportionality analysis， information component （IC） and reporting odds ratio （ROR）， were applied in nivolumab-associated pulmonary adverse events （AEs） signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably， potent signals were detected in radiation pneumonitis （IC025： 3.99， ROR025： 17.25）， pneumonitis （IC025： 3.34， ROR025： 10.64） and bronchial fistula （IC025： 2.94， ROR025： 8.78）. Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea （IC025： 0.50， ROR025： 1.44）， pneumonia （IC025： 0.08， ROR025： 1.07） and pneumonitis （IC025： 3.34， ROR025： 10.64）. Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer （N=3 711， 32.13%）， malignant melanoma （N=1 658， 14.36%） and renal cell carcinoma （N=731， 6.33%）. Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus， it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.

Haematological toxicity in cancer cervix patients treated with concurrent chemoradiation by conventional technique- correlation with bone marrow radiation dose

Introduction: The standard of care for treatment of cancer cervix is concurrent chemoradiation followed by brachytherapy in the majority of cases. Conventional radiotherapy with chemotherapy causes haematological toxicities which may be related to radiation to pelvic bone marrow. The present study aims to study the haematological toxicities and correlate with the mean dose to the bone marrow. Material and Methods: Retrospective data of cancer patients treated in the institute in the year 2019 was retrieved. Haematological toxicities were analyzed in terms of CTCAE criteria. Mean dose to bone marrow was calculated after the delineation in the CT scan. The correlation between haematological toxicity and mean bone marrow was done using a paired t-test for statistical significance. Results: The data of 20 patients were retrieved. Anaemia Grade, I and Grade II-IV was seen in 65% and 35% respectively. Leukopenia Grade I and Grade II-IV were seen in 85% and 15% respectively and Lymphopenia Grade I and Grade II-Iv were seen in 55% and 45% respectively. The mean dose to bone marrow did not show any statistical significance with the severity of haematological toxicity. There was no Grade II-IV toxicity of neutropenia and thrombocytopenia. Conclusion: Conventional radiotherapy can safely be practice for patients with cancer cervix with acceptable haematological toxicities.

Effect of glutamine supplement on chemo-radiation induced mucositis in head and neck cancer patients: a prospective study

Background: Radiotherapy is one of the primary modalities of cancer treatment but may associated with short and long-term toxicities. Oral mucositis is frequently encountered in head and neck cancer resulting in unplanned treatment breaks. Few studies emphasized that use of oral glutamine may significantly reduce oral mucositis and other acute toxicities. This study aims to assess the effects of glutamine on oral mucositis in head and neck cancer patients receiving chemo-radiation.Methods: It is a prospective study carried out in sixty-four head and neck cancer patients attending radiotherapy department for chemo-radiation from January 2018 to May 2019. Patients were randomly assigned into two arms containing 32 subjects in each. All the patients in arm-A were taking oral glutamine supplement of 15 mg once daily, two hours prior to radiation and arm-B serve as the control group. Dose of radiation fixed at 66 Gy in 33 fractions over a period of 7 weeks along with an infusion of weekly cisplatin (40 mg/m2). Patients were evaluated regarding onset, severity and the recovery period of mucositis.Results: Oral mucositis appeared at around 5th week in arm-A and 3rd week in arm-B (p<0.0001). Number of patients with mucositis is significantly less in arm-A (75%, 24 out of 32) as compared to arm-B (96.8%) (p=0.0310). The time required for healing of mucositis is significantly less than 1 week in arm-A compared to ~2 weeks in the arm-B (p<0.0001).Conclusions: Oral glutamine when given prior to radiation results in delayed onset of oral mucositis with decreased severity and an early healing period.

Concurrent chemoradiation in head and neck cancers with weekly cisplatin: analysing toxicities

Background: Head and neck cancers constitute 6% of cancers worldwide. The management requires a multidisciplinary approach. Concomitant chemoradiotherapy with cisplatin is the standard approach for locally advanced head and neck cancers. The most commonly used regime uses three weekly cisplatin which is more toxic. Low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience.  Methods: Squamous cell carcinoma of stage III, IVA and IVB of oropharynx, hypopharynx and larynx were studied for one year. 82 patients were studied. Total dose of radiation was 66Gy/33#/6 ½ weeks from Monday to Friday with inj. Cisplatin 40mg/m2 i.v. infusion weekly.Results: 88% of patients were able to complete five or more weekly chemotherapy cycles with cumulative dose of 200mg/m2. Grade 2 and 3 acute toxicities were seen in weekly cisplatin arm but were conservatively managed.Conclusions: Weekly cisplatin can be used with concurrent radiotherapy as the acute toxicities are manageable and is well tolerated.

Clinico-epidemiological Profile Of Patients With Gynaecological Malignancies Being Followed-up At A Radiation Oncology Department Of A Tertiary Care Government Institute Of India

Background: Gynaecological malignancies constitute a major burden of cancer-related morbidity and mortality amongst females in developing countries including India. Aims and objectives: The study was conducted to study the clinical and morphological characteristics of patients having gynaecological malignancies and treated by radiotherapy with or without chemotherapy, now under follow-up. Study design: Aretrospective observational study in a tertiary care hospital of government set-up over 2 year period. Observations: A total of 3120 patients who reported for follow-up were included, of which 394 patients were of gynaecological malignancies. Carcinoma (Ca) Cervix followed by Ca endometrium were the most common sites (76% and 16% respectively). The most common age group was 7th decade. 33% patients with locally advanced cervical cancer were found to have paraaortic lymphadenopathy on presentation warranting extended field radiotherapy (RT). 73% of locally advanced ca cervix patients received 5 or more cycles of weekly chemotherapy (CT) with Cisplatin. 68% patients were disease-free at the time of follow-up. 11% patients were referred for palliative chemotherapy. 17% patients required hospitalization for symptomatic care during followup. Conclusion: Concurrent chemoradiation is an acceptable and well-tolerated modality of treatment for locally advanced gynaecological malignancies. Multimodal treatment and good collaboration between allied specialists is recommended.

Conventional Radiotherapy with Hypofractionated Radiotherapy in Post-Mastectomy Breast Cancer Patients: A Prospective Comparative Study

Aim: The aim of this study is to assess the efficacy, toxicity, and feasibility of hypofractionated radiotherapy in post-mastectomybreast cancer patients compared with conventional radiotherapy.Materials and Methods: A total of 80 post-mastectomy breast cancer patients were randomized into two groups for adjuvantradiotherapy. Control group of 40 patients received conventional radiotherapy of 50 GY in 5 weeks. Study group of 40 patientsreceived hypofractionated radiotherapy of 42.72 GY in 3.1 weeks.Results: The statistical analysis of the study was performed in terms of tolerability, radiation toxicities, and feasibility of thehypofractionated radiotherapy over conventional radiotherapy. There was found to be no significant difference between thetwo groups.Conclusion: In breast cancer patients after post-mastectomy, hypofractionated radiotherapy in comparison to conventionalradiotherapy finds comparable outcomes without any significant difference in radiation-induced toxicities.

Radiotherapy and geriatric cancer patients: A single institute experience

OBJECTIVES:The aim of this study was to study patient, disease, and treatment related characteristics in geriatric patients 65 years and older treated by Radiotherapy (RT).MATERIAL AND METHODS:A retrospective observational and descriptive study was conducted in a tertiary care gov- ernment institute with academic and research potential. The electronic medical records, medical documents, and Radiotherapy treatment charts were retrieved and studied.RESULTS:247 patients aged 65 years and older were included over 2-year study period. Mean age was 70.3 years and the oldest patient treated was of 94 years. 66% patients were males. 82 patients (33%) had metastatic disease. The common sites of origin were head and neck (28%), lung (23%), genitourinary (20%), and gastrointestinal malig- nancies (15%). 125 patients (51%) were having one or more co-morbidities. 135 patients (55%) were treated with radical intent. 66 patients (27%) received chemotherapy in concurrent setting. 89 patients (36%) were hospitalized for some duration of their RT course. In 58 patients (23%), RT was interrupted briefly. 46 patients (19%) could not complete the prescribed RT. 8 patients (3%) developed Grade 3 and 4 hematological toxicities. 57% patients developed Grade 2,3 mucocutaneous toxicities. 53% patients developed Grade 2,3 GI toxicities. Mortality rate while on treatment was 4%.CONCLUSION:Geriatric patients, though more prone to develop systemic and site-specific toxicities warranting supportive care in indoor or outdoor setting, can be offered Radiotherapy either alone or concurrently with che- motherapy. Such patients present with heterogeneous spectrum of entities often posing a therapeutic challenge to clinicians; but proper selection of cases and diligent supervision may allow these patients to be treated with Radiotherapy with radical or palliative intent as indicated.

Efficacy and prognosis of radiotherapy for patients with postoperative pelvic recurrence in uterine cervical cancer / 中华放射医学与防护杂志

Objective To analyze the result and adverse reactions of radiation therapy in patients with pelvic recurrence following cervical cancer postoperative.Methods A retrospective analysis of 147 patients with pelvic recurrence after surgical treatment of cervical cancer in the Fourth Hospital of Hebei Medical University from August 2004 to December 2016 was performed.All patients received radiotherapy with or without chemotherapy.According to different clinical factors and pathological factors,Logistic regression analysis was used to analyze the factors influencing radiotherapy outcomes in patients with pelvic recurrence after cervical cancer surgery.The Kaplan-Meier method was used to analyze the survival rate,and the corresponding survival curve was drawn.The survival rate and prognosis related factors were compared by using the log-rank test.The COX proportional hazards regression model was used for multivariate analysis of statistically relevant factors in univariate analysis.After treatment,toxicities were analyzed using chi-square test.Results The median follow-up time was 33.2 months.95％ of the patients completed radiation therapy with a dose of ≥ 67 Gy (median radiotherapy dose),and 91 patients (61.9％) had complete remission (CR).The 5-year local control (LC),progression-free survival (PFS),distant metastasis-free survival (DMFS),and overall survival (OS) were 63.6％,56.0％,73.9％,and 55.0％,respectively.Univariate logistic regression analysis showed that FIGO staging (stage 0-ⅠB and ⅡA-ⅡB),pelvic sidewall involvement,and recurrent tumor volume were associated with complete remission (P＜0.05).Multivariate statistical analysis found that FIGO staging and pelvic sidewall invasion were independent factors influencing the efficacy and survival of patients with pelvic recurrence after cervical cancer surgery (P＜0.05).Patients with pelvic wall invasion after cervical cancer surgery had a higher incidence of ≥ grade 2 proctitis than those without pelvic walls involved,which were 26.9％ and 16.7％,respectively.Conclusions This study shows that after the surgical treatment of cervical cancer patients with pelvic recurrence can be tolerated by toxicities after radiation therapy.In addition,the incidence of toxicities in patients with pelvic wall invasion was significantly higher than those without pelvic wall invasion.Preoperative staging and the pelvic wall involvement are independent influencing factors influencing the effect of radiotherapy and long-term prognosis in patients with pelvic recurrence after cervical cancer surgery.

Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors / 中国肺癌杂志

The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

Clinical Diagnosis and Treatment Recommendations for the Pneumonitis Associated with Immune Checkpoint Inhibitor / 中国肺癌杂志

The increasing use of immunocheckpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immunocheckpoint inhibitors, mainly activated T-cell immunity, may attack normal tissues and organs of the human body and lead to a variety of adverse effects. In the lung, they could induce checkpoint inhibitor associated pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and had a potentially fatal risk if it was not being properly treated. We will summarize the characteristics of CIP and give our advice on how to manage immunocheckpoint inhibitor associated pneumonitis.

Clinical Diagnosis and Treatment Recommendations for Cardiac Adverse Reactions Related to Immune Checkpoint Inhibitor / 中国肺癌杂志

Immunotherapy of malignant tumors has become a hot spot in the field of cancer research and treatment, bringing new hope to patients with advanced cancer. Activation of molecular programmer death protein-1 and T lymphocyte-associated antigen 4-related signaling pathways at the immunological checkpoint can inhibit T lymphocyte activation and thereby block the inflammatory response. Tumor cells achieve immune escape by activating the molecular pathways associated with immune checkpoints. The immune checkpoint inhibitor can wake up T lymphocytes and enhance the body's clearance of tumor cells. However, the role of immune checkpoint inhibitors is not specific to tumor cells, and it can cause side effects of multiple systems including the cardiovascular system while killing tumor cells. We will summarize the relevant cardiac side effects and give advice on how to manage it.

Management of Dermatologic Toxicities Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Dermatologic toxicities appear to be one of the most prevalent irAEs. The most common symptoms are maculopapular rash and pruritus. Serious dermatologic AEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, are rare. In this review, we summarized guidelines of management of immunotherapy-related toxicities and case reports, and proposed treatment recommendation.

Clinical Diagnosis and Treatment Recommendations for Ocular Toxicities of Target Therapy and Immune Checkpoint Inhibitor Therapy / 中国肺癌杂志

The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.

A prospective clinical study of early breast cancer treated with hypofractionated simultaneous integrated boost IMRT/ VMAT after breast conservative surgery / 中华放射医学与防护杂志

Objective@#To evaluate the efficacy, toxicity and cosmetic outcomes of hypofractionated simultaneous integrated boost intensity-modulated radiotherapy (IMRT-SIB) after breast conservative surgery (BCS) for early breast cancer patients.@*Methods@#A total of 76 patients with stage TisT1-2N0M0 breast cancer treated with BCS were enrolled in the analysis. The patients who underwent breast radiotherapy without regional lymph node irridiation and hypo fractionated IMRT/VMAT were used. All patients received whole breast IMRT/VMAT with tumor bed SIB. The doses delivered to the whole breast was 42.4 Gy in 16 fractions, and the dose delivered to tumor bed for SIB was 49.6 Gy in 16 fractions. Cosmetic evaluation was based on the Harvard system. Acute and late toxicities were scored according to CACAT version 3.0. Survival and recurrence rates were calculated by Kaplan-Meier method. The univariate and multivariate analysis were conducted with logistic regression.@*Results@#The median follow-up was 29 months (range 16-40 months). The follow-up rate was 100%. The 1-, 2-and 3-year overall survival rates were 100%. No recurrence or metastasis was observed in this study. The incidence of grade 1 acute skin toxicity was 68.4%, grade 2 was 7.9%. The late skin toxicity of grade 1 was 13.1%, grade 2 was 2.6%.In all, 82.4% of patients had excellent and good cosmetic outcome. The Mean dose of the tumor bed was predictive factor for grade 2 dermatitis.@*Conclusion@#The efficacy, cosmetic effect, the acute and late treatment-related toxicity of hypofractionated IMRT/VMAT-SIB in patients with early breast cancer following BCS might be acceptable. A longer follow-up is needed to define the efficacy on outcomes.@*Trial registration@#Chinese clinical trial registry, ChiCTR1800016287

Association of the therapeutic efficacy and toxicity of Morphine with polymorphism of drug metabolism-related genes in the treatment of cancer pain / 中华老年医学杂志

Objective To investigate the relationship of OPRM1 C354A mutations with the clinical efficacy and toxicity of Morphine in the treatment of cancer pain.Methods We recruited 100 patients with moderate-severe cancer pain treated at our department from January 2016 to December 2016,and divided them into a CA(wild type homozygotes) group,a CG(mutated heterozygotes) group,and a GG (homozygous homozygous) group,according to the allele type of OPRM1 C354A.Regular analgesic doses of Morphine were given to all groups,and VAS scores and adverse reactions at 2,4,8,16,24,aud 48 hours after analgesia were collected and compared among the groups.Results The (OPRM1 C354A mutation groups(CG+GG)had lower VAS scores at every time point,compared with those of the non-mutation group(CA) (2 h:3.61±0.39 vs.4.04±0.52;4 h:3.88±0.41 vs.4.20± 0.15;8 h:3.95±0.32 vs.4.37±0.24;16 h:3.81±0.38 vs.4.33±0.15;24 h:3.84±0.25 vs.4.42± 0.18;and48 h:3.86±0.20 vs.4.41± 0.14) (t=4.648,5.261,7.461,8.454,13.389,and 16.030,respectively,each P=0.000).The incidences of constipation(23.08％ vs.6.25％)and vertigo(25％ vs.8.33％)in the OPRM1 C354A mutation groups(CG+GG)were significantly higher than those in the non-mutation group(CA) (x2 =5.543 and 4.914.P=0.019 and 0.027,respectively).Conclusions Polymorphism of the (PRM1 C354A gene is associated with the clinical efficacy and toxicity of morphine in the treatment of cancer pain.

Involved field irradiation(IFI)versus elective nodal irradiation(ENI)in combination with concurrent chemotherapy for esophageal thoracic squamous cell cancer:a prospective,randomized, multicenter,controlled study / 中华放射肿瘤学杂志

Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.