Successful continuous nivolumab therapy for metastatic non‐small cell lung cancer after local treatment of oligometastatic lesions
Satoshi TobitaYuhei KineharaYoshio TamuraHiroyuki KurebeRyusuke NinomiyaYoshihiko UtsuSatoshi KohmoBunzo SatoKenichi NagaiShintaro MaruokaRyu JokojiShohei KoyamaIsao Tachibana
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Abstract The patient in this report was a 57‐year‐old man with metastatic non‐small cell lung cancer (NSCLC). After no response to two lines of systemic chemotherapy, he was treated with nivolumab as third‐line therapy, which resulted in a partial response. After 17 months of nivolumab treatment, he developed bone metastasis in his left femur which was treated with radiation therapy. Nivolumab was restarted after radiation therapy. Four months after radiation therapy, he developed another metastatic lesion in the small intestine which was surgically resected. Because there were no recurrent NSCLC lesions after surgical resection, nivolumab was restarted again. At 18 months after surgery, there were no recurrent NSCLC lesions. Immunohistochemical analysis of peritumoral T lymphocytes showed higher expression of T cell immunoglobulin and mucin domain‐containing protein 3 (TIM‐3) and lymphocyte activation gene 3 (LAG‐3) in recurrent lesions of bone and small intestine than in primary lesions. Upregulation of TIM‐3 and LAG‐3 could be associated with mechanisms of adaptive resistance to nivolumab in this case. Here, we report a successful case of continued nivolumab therapy with remission after local treatments consisting of radiation therapy and surgical resection for oligometastases. Continuation of immune checkpoint inhibitor (ICI) treatment may be worth considering if oligometastases can be controlled. Key points Significant findings of the study We report a successful case of continued nivolumab treatment with remission after local treatment (radiation therapy and surgical resection) for oligometastases. What this study adds Upregulation of T cell immunoglobulin and mucin domain‐containing protein 3 and lymphocyte‐activation gene 3 could be associated with mechanisms of adaptive resistance to nivolumab.Abstract Background Nivolumab plus ipilimumab has demonstrated improved survival for treatment-naïve advanced clear cell renal cell carcinoma (RCC). A series of clinical trials evaluated the effect of salvage nivolumab plus ipilimumab in patients without an objective response to nivolumab. Given the size and heterogeneity of these studies, we performed a pooled analysis to better inform the activity of nivolumab plus ipilimumab after nivolumab. Patients and Methods Eligible patients included those with advanced clear cell RCC having received no prior immunotherapy. The primary objective was confirmed objective response rate (ORR) by investigator-assessment. Secondary objectives included progression-free survival (PFS) and overall survival (OS). Results The analysis included 410 patients with clear cell RCC, of whom 340 (82.9%) had IMDC intermediate/poor risk disease, and 137 (33.4%) had prior treatment. The 16-18-week ORR to nivolumab prior to nivolumab plus ipilimumab was 22.7% (n = 93), and best ORR to nivolumab was 25.1% (n = 103). Two hundred and thirty (56.1%) patients treated with nivolumab received nivolumab plus ipilimumab at a median of 16 weeks (IQR 9-19) after initiation of nivolumab [27.0% (n = 62) with stable disease and 73.0% (n = 168) with progressive disease to nivolumab]. The ORR to nivolumab plus ipilimumab was 12.6% (n = 29). Six-month PFS on nivolumab plus ipilimumab was 37% (95% CI, 27-47). Median follow-up was 34.3 months and 3-year OS was 59% (95% CI, 53-64) from nivolumab start. Conclusion A small subset of patients lacking a response to nivolumab derive benefit from salvage nivolumab plus ipilimumab. When possible, both drugs should be given in concomitantly, rather in an adaptive fashion.
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Objective:To investigate the clinical features in patients with NKTLNT,the treatment response between radiotherapy as initial treatment and chemotherapy as initial treatment,and the influence of different therapy on 5-year survival.Methods:The deta of 57 patients with Ann Arbor stage IE NKTLNT who underwent radiotherapy+chemotherapy,or chemotherapy+radiotherapy,were retrospectively reviewed.These patients were divided into two groups according to initial treatment:radiotherapy alone or radiotherapy+chemotherapy group(n=35 patients) and a chemotherapy+radiotherapy group(n=22 patients).The treatment response,and survival data for the patients were compared between this two groups.Results:There was no significant difference in the clinical profiles between the two groups.26 patients(74%) in the radiotherapy plus chemotherapy group achieved complete response after initial treatment,whereas only 5 patients(23%) in the chemotherapy plus radiotherapy group achieved complete response.But Compared with the patients in the chemotherapy+radiotherapy group,those in the radiotherapy+chemotherapy group had a similar 5-year overall survival rate(61.9% for the radiotherapy+chemotherapy group vs.55% for the chemotherapy+radiotherapy group).Conclusions:NKTLNT do not have specific symptoms which can help for early-stage diagnosis,and radiotherapy as initial treatment can achieve better treatment response,but our research does not get an increased 5-year overall survival rate in the radiotherapy+ chemotherapy group.
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Blood stasis syndrome,which commonly exists in patients with malignant tumor,is not only a objective sign in cancer,but also plays an important role in the growth,invasion and metastasis of malignant tumor. Operation,radiotherapy and chemotherapy are the main treatments of cancer and all of these three treatments can reduce the tumor and relieve the symptoms.Therefore,operation,radiotherapy and chemotherapy can ease the patients' blood stasis state to a certain extent. However,operation,radiotherapy and chemotherapy may cause some damage to the body and can effect the stasis syndrome in the different time of treatment process. So,operation,radiotherapy and chemotherapy may have the potential promote to the invasion and metastasis of malignant tumor through effect the blood stasis state. Therefore,using blood-activating herbs in the different time of operation,radiotherapy and chemotherapy may have different effects on the tumor invasion and metastasis.
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Objective To retrospectively analyze and evaluate the outcome of malignant cerebral glioma treated by chemotherapy plus radiotherapy.Methods A total of 126 patients with malignant cerebral glioma were retrospectively studied.Sixty-four patients in the radiotherapy group were irradiated with DT54-60 Gy,62 patients in the chemotherapy plus radiotherapy group were given chemotherapy(VM-26 and Me-CCNU)after exposure to DT 20 Gy.The 1-,3-and 5-year survival rates of these patients were compared.Results The 1-,3-,and 5-year survival rates of the radiotherapy group were 64.06%,31.25%,and 15.63% respectively,while the 1-,3-,and 5-year survival rates of the chemotherapy plus radiotherapy group were 80.65%,50%,and 30.65 % respectively(P 0.05).Conclusion Combination of chemotherapy and radiotherapy is effective and well-tolerated in the treatment of malignant cerebral glioma.
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Breast cancer is one of the most common malignancies in women worldwide. It can be treated with surgery combined with chemotherapy and radiotherapy.This study aims to investigate the effects of chemotherapy and radiation therapy on blood cell components of breast cancer patients who survived one of these therapies, in Al-Amal National Hospital for Cancer Management. Numbers of blood cells including white blood cell (WBC), red blood cell (RBC) and lymphocytes, and hemoglobin (HGB) concentration were measured in thirty-two women with eighteen of them treated with chemotherapy and the left treated with radiotherapy.The results showed that the counts of WBC, RBC and lymphocytes decreased faster in the patients treated with chemotherapy compared to that in the patients treated with radiotherapy, whereas HGB concentrations only slightly changed with both treatments, upon four cycles of each treatment. These results support that radiotherapy may cause less side effects on breast cancer patients compared to chemotherapy.
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Induction chemotherapy, followed by surgery and/or radiotherapy was utilized in patients with advanced squamous cell carcinoma of the head and neck. During these trials, the authors observed that response to chemotherapy predicts further response to subsequent radiotherapy. This study was comprised of 57 patients with 60 separate neoplasms who demonstrated less than complete response (partial or no response) to initial treatment with a combination chemotherapy containing cisplatin. Subsequently radiotherapy, either 5000 rad preoperatively or 6600 rad as definitive therapy, was employed. Forty-one of the 42 tumors with initial partial response to chemotherapy also responded to radiotherapy (97.6%). Only one of the 18 tumors that initially failed to respond to chemotherapy subsequently responded to radiotherapy (5.5%). This observation suggests that patients with head and neck cancer sensitive to initial chemotherapy share parameters that are also radiation sensitive.
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Abstract Background Nivolumab is an anti‐PD1 immune checkpoint inhibitor commonly used for the treatment of solid organ and hematological malignancies. Severe infusion reaction due to nivolumab is quite rare. Case We report a case of severe infusion reaction due to nivolumab necessitating ICU admission and withdrawal of further nivolumab use in a patient with metastatic non‐small cell lung cancer. Conclusion Our knowledge and expertise with the use of immune checkpoint inhibitors are still evolving. This report highlights one of the rare possible side‐effects that clinicians and patients may have to face with increasing indications and use of nivolumab in day to day practice.
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Until now, the possibility of radiotherapeutic treatment after a failure of chemotherapy has not been systematically investigated. Eight cases with primary failure of chemotherapy or recurrence after chemotherapy could be evaluated. The patients were submitted to curative irradiation; six of them achieved a total remission, four had recurrences. Thus two patients remain to give an example that radiotherapy can bring about long-term total remissions after primary failure of chemotherapy or recurrence after chemotherapy. When the data were evaluated, the total remission times of the two patients were 12 and 18 months, respectively. The toxicity of radiotherapy was justifiable. It was increased especially in regions that had already been irradiated or if a ABVD therapy was applied a short time before or after the radiotherapy. There are only few communications in literature about the success of a radiotherapy after failure of chemotherapy. Most of the patients mentioned had "remissions" (total/partial remissions?). In most of the cases, there are no indications about the further development. On the whole, the data show that there may be some special indications for radiotherapy in case of a failure of chemotherapy.
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Objective:To study the changes of platelet parameter in tumor patients before or after radiotherapy and chemotherapy and the clinic significance.Methods: 31 cases of tumor patients before or after radiotherapy and chemotherapy were selected and their platelet parameters(PLT,PCT,MPV,DPW,P-LCR) were measured by the sysmex SF-3000 complete automatic hemanalysis, then compared with control group.Results: There was no signficant difference between the two groups in the platelet parameters before radiotherapy and chemotherapy(P0.05).The levels of PLT,PCT,MPV,P-LCR in tumor patients after radiotherapy and chemotherapy were significantly lower than that before radiotherapy and chemotherapy(P0.01或P0.05),but PDW is no different(P0.05).Conclusion:Determine of platelet parameters of tumor patients before or after radiotherapy and chemotherapy is of certain clinical significance for observation of the status of their marrow restrained and estimate of state of illness.
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