A Case of Thymic Carcinoma That Achieved a Long-term Progression-free Survival by Radiation Therapy and Sequential Chemotherapy for Postoperative Intrathoracic Recurrence

Object Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. Methods Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. Results The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9–416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). Conclusions This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

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ABVD Chemotherapy Results in Excellent Outcomes with Reduced Radiation Therapy Rates in Children, Adolescents and Young Adults with Hodgkin Lymphoma

Blood ◽

10.1182/blood.v126.23.2695.2695 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2695-2695

Author(s):

Kristin C. Marr ◽

Joseph M. Connors ◽

Karen J. Goddard ◽

Kerry J. Savage ◽

Rebecca J. Deyell

Keyword(s):

Overall Survival ◽

Young Adults ◽

Radiation Therapy ◽

Research Funding ◽

Progression Free Survival ◽

Advanced Stage ◽

Free Survival ◽

Limited Stage ◽

Stage Disease

Abstract BACKGROUND Hodgkin lymphoma (HL) incidence peaks in adolescence and young adulthood. The care of patients in this age range must address unique challenges as it spans the transition from pediatric to adult centers and treatment approaches vary considerably. The current standard of care for treatment of HL in adults is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with varying use of consolidation radiation therapy (RT). Multiple large trials in adults have demonstrated excellent long-term survival outcomes for both limited and advanced stage disease, with low rates of long-term toxicity. In British Columbia, Canada, ABVD was adopted for primary treatment of HL in the pediatric population in 2004. Pediatric, adolescent and young adult outcomes following this approach, in combination with reduced rates of RT, have not been reported. We report outcomes of a population-based cohort of children (age <18y) and young adults (18-25y at diagnosis) with HL who received a standardized ABVD regimen across adult and pediatric centers. PATIENTS AND METHODS The study cohort included 222 patients (n=58 < 18y; n=164 18-25y) with all histological subtypes of HL diagnosed from January 1, 2004 to July 1, 2013 who received ABVD as initial therapy. 87 patients had limited stage (IA, IB, IIA, bulk < 10 cm) and 135 had advanced stage disease (IA-IIA with bulk >10 cm and IIB-IVB). Limited stage patients received 2 cycles of ABVD followed by PET/CT assessment. Consolidation treatment consisted of involved-field radiation therapy (IFRT) to the area of original disease for incomplete responders (PET positive) or 2 further cycles of ABVD. Advanced stage patients were treated with 6 cycles of ABVD followed by repeat imaging. IFRT to areas of residual disease (PET positive and/or persistent mass by CT scan) was recommended for those patients with incomplete response. RESULTS There were no significant differences in gender, histology, B symptoms or bulk between children (< 18y) and young adults (18-25y). The pediatric group had higher proportions of Ann Arbor stage III or IV disease (p =.002), possibly related to more frequent use of PET/CT scanning for staging (66% vs 10%, respectively, p= <.001), but the groups were similar following risk stratification into limited (36% vs 40%, respectively) and advanced (64% vs 60%, respectively) stage disease (p =.588). The median follow-up was 64 months. More young adults achieved complete response at end of therapy (95% vs 83%; p =.004). Children were more likely to have primary progressive disease with 9 of 11 treatment failures (82%) occurring during treatment or within 6 months of completion. Patients aged 18-25y were more likely to have late treatment failures, with 41% of relapses occurring greater than 12 months after therapy completion (p =0.014). There were no toxicity-related deaths. The 5 year overall survival (OS) and progression-free survival (PFS) for the entire cohort (n=222) were 97±1% and 84±3%, respectively. In limited stage disease, OS and PFS were 100% and 91±3%, while those with advanced stage had an OS of 95±2 % and PFS of 80±4%. There was no difference in OS (93±4% vs 98±1%, p =.120) or PFS (81±5% vs 85±3%, p =.222) between children and young adults. The rate of consolidative RT was 20% overall (24% in limited stage; 18% in advanced stage) with no difference between age groups (p =.295). CONCLUSION ABVD is an effective treatment for HL in the pediatric, adolescent and young adult populations. Radiation therapy can be omitted for the 75% of patients who achieve a complete response to chemotherapy while maintaining comparable 5 year overall survival outcomes, thus limiting the risk of radiation related long-term toxicities. Figure 1. Overall Survival and Progression-Free Survival for Whole Cohort Figure 1. Overall Survival and Progression-Free Survival for Whole Cohort Figure 2. Overall Survival and Progression-Free Survival by Risk Group and Age Group Figure 2. Overall Survival and Progression-Free Survival by Risk Group and Age Group Disclosures Connors: Roche: Research Funding; Seattle Genetics: Research Funding. Savage:Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding.

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Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

Journal of Investigative Medicine ◽

10.1136/jim-2020-001650 ◽

2021 ◽

Vol 69 (4) ◽

pp. 888-892

Author(s):

Joseph I Clark ◽

Brendan Curti ◽

Elizabeth J Davis ◽

Howard Kaufman ◽

Asim Amin ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Melanoma ◽

Systemic Therapy ◽

Renal Cell ◽

Interleukin 2 ◽

Progression Free Survival ◽

High Dose ◽

Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

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Hyperfractionated Radiation Therapy With or Without Concurrent Low-Dose Daily Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Prospective Randomized Trial

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.7.1458 ◽

2000 ◽

Vol 18 (7) ◽

pp. 1458-1464 ◽

Cited By ~ 345

Author(s):

Branislav Jeremic ◽

Yuta Shibamoto ◽

Biljana Milicic ◽

Nebojsa Nikolic ◽

Aleksandar Dagovic ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Radiation Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Low Dose ◽

Locally Advanced ◽

Progression Free Survival ◽

High Grade ◽

Free Survival

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.

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A phase I/Ib trial targeting the Pi3k/Akt pathway using perifosine: Long-term progression-free survival of patients with resistant neuroblastoma

International Journal of Cancer ◽

10.1002/ijc.30440 ◽

2016 ◽

Vol 140 (2) ◽

pp. 480-484 ◽

Cited By ~ 23

Author(s):

Brian H. Kushner ◽

Nai-Kong V. Cheung ◽

Shakeel Modak ◽

Oren J. Becher ◽

Ellen M. Basu ◽

...

Keyword(s):

Phase I ◽

Progression Free Survival ◽

Akt Pathway ◽

Free Survival

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Long-term outcomes in children with glioblastoma

Journal of Neurosurgery Pediatrics ◽

10.3171/2010.5.peds09558 ◽

2010 ◽

Vol 6 (2) ◽

pp. 145-149 ◽

Cited By ~ 50

Author(s):

Kyung Sun Song ◽

Ji Hoon Phi ◽

Byung-Kyu Cho ◽

Kyu-Chang Wang ◽

Ji Yeoun Lee ◽

...

Keyword(s):

Radiation Therapy ◽

Progression Free Survival ◽

Radical Resection ◽

Tumor Location ◽

Recurrent Glioblastoma ◽

Subtotal Resection ◽

Long Term Outcomes ◽

Term Outcome ◽

Long Term Outcome

Object Glioblastoma is the most common primary malignant brain tumor; however, glioblastoma in children is less common than in adults, and little is known about its clinical outcome in children. The authors evaluated the long-term outcome of glioblastoma in children. Methods Twenty-seven children were confirmed to have harbored a glioblastoma between 1985 and 2007. The clinical features and treatment outcomes were reviewed retrospectively. All patients underwent resection; complete resection was performed in 12 patients (44%), subtotal resection in 12 patients (44%), and biopsy in 3 patients (11%). Twenty-four patients (89%) had radiation therapy, and 14 (52%) patients received chemotherapy plus radiation therapy. Among the latter, 5 patients had radiation therapy concurrent with temozolomide chemotherapy. Four patients with small-size recurrent glioblastoma received stereotactic radiosurgery. Results The median overall survival (OS) was 43 months, and the median progression-free survival was 12 months. The OS rate was 67% at 1 year, 52% at 2 years, and 40% at 5 years. The median OS was significantly associated with tumor location (52 months for superficially located tumors vs 7 months for deeply located tumors; p = 0.017) and extent of removal (106 months for completely resected tumors vs 11 months for incompletely resected tumors; p < 0.0001). Conclusions The prognosis of glioblastoma is better in children than in adults. Radical resection followed by concurrent chemoradiation therapy may be the initial treatment of choice.

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A phase II study of anlotinib plus whole brain radiation therapy (WBRT) for advanced non-small cell lung cancer with multiple brain metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21063 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21063-e21063

Author(s):

Xiangzhi Zhu ◽

Hua Tao ◽

Ming Jiang ◽

Meiqi Shi ◽

Cheng Kong ◽

...

Keyword(s):

Lung Cancer ◽

Radiation Therapy ◽

Brain Metastases ◽

Advanced Nsclc ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Multiple Brain Metastases ◽

Common Grade

e21063 Background: The prognosis of non-small-cell lung cancer (NSCLC) patients(pts) with multiple brain metastases is poor. WBRT is the main treatment for the pts, but QUARTZ study showed that the efficacy of WBRT is unsatisfactory. The synergistic effect of the antiangiogenic therapy with radiation therapy has been well established. Anlotinib, an antiangiogenic multi-target TKI, had significantly improved progression-free survival (PFS) of advanced NSCLC with Brain Metastases. This study aimed to evaluate the efficacy and safety of anlotinib combined with WBRT in pts with brain metastases ( > 3) from advanced NSCLC. Methods: Advanced NSCLC pts with brain metastases ( > 3) who were histologically confirmed to be driver gene wild type or positive and pts who had received two or more previous treatments were eligible. Pts with meningeal metastasis were excluded. All pts were treated with anlotinib (12 mg, QD, day 1 to 14 of a 21-day cycle) combined with WBRT (DT 30Gy/12f), followed by maintenance therapy with anlotinib until disease progression or treatment intolerance. The primary endpoint was intracranial progression-free survival (iPFS). Secondary endpoints were extracranial PFS (ePFS), OS and toxicity. Results: As of 25 Jan 2021, 28 pts were enrolled. The median age was 57.5 years with 46.4% male. 89.3% of pts with adenocarcinoma. 21.4% pts harbored EGFR mutation. A total of 25 pts were included in efficacy analysis. In intracranial evaluation, ORR was 64.0%, DCR was 88.0%, median iPFS was 11.1 months (95% CI 5.9 to 12.1). In extracranial evaluation, ORR was 12.0%, DCR was 84.0%, median ePFS was 6.0months (95% CI 3.2 to 8.8). Most common grade 1-2 adverse events (AEs) were hypertension (67.8%), fatigue (64.2%)，anorexia (46.4%) and hand and foot skin reaction (37.5%). The most common grade 3-4 AEs were hypertension (12.5%), hand and foot skin reaction (10.7%) and fatigue (7.2%). No intracranial hemorrhage occurred during treatment. Dose adjustment due to AE occurred in 21.4% patients. Conclusions: This prospective study shows that the combination of anlotinib and WBRT for patients with multiple brain metastases after standard treatment resistance exhibited an effective therapeutic approach and manageable AEs. For further investigation, large sample and additional clinical trials are warranted. Clinical trial information: ChiCTR1900022093.

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Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumours

Endocrine Related Cancer ◽

10.1530/erc-21-0034 ◽

2021 ◽

Author(s):

Ophelie De Rycke ◽

Thomas Walter ◽

Marine Perrier ◽

Olivia Hentic ◽

Catherine Lombard-Bohas ◽

...

Keyword(s):

Neuroendocrine Tumours ◽

Objective Response ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Tumor Control ◽

Free Survival ◽

Mgmt Expression ◽

Pancreatic Neuroendocrine Tumours

A rechallenge is common after initial efficacy of alkylating-based chemotherapy (ALK) in pancreatic neuroendocrine tumors (PanNET). High MGMT expression seems associated with lower response to ALK. We aimed to evaluate the efficacy and toxicity of ALK rechallenge in PanNET. Secondly, to assess the evolution of MGMT expression under ALK. All consecutive patients with advanced PanNETs who received initial ALK (achieving tumor control) followed by a pause > 3 months, then an ALK rechallenge (ALK2) upon progression were retrospectively studied (Cohort A). Primary endpoint was progression-free survival under ALK2 (PFS2). The MGMT expression was retrospectively assessed by immunohistochemistry (H-score) in consecutive PanNET surgically resected following ALK (Cohort B). We foud that cohort A included 62 patients (median Ki67 8%), for which ALK1 followed by pause achieved an objective response rate of 55%, and a PFS1 of 23.7 months (95% IC, 19.8-27.6). ALK2 achieved no objective response, and stability in 62% of patients. The median PFS2 was 9.2 months (IC 95% 7.1-11.3). At multivariable analysis, a hormonal syndrome (p=0.032) and a pause longer than 12 months (p=0.041) were associated with a longer PFS2. In the cohort B (17 patients), the median MGMT H-score increased from 45 (IQR 18-105) before ALK, to 100 (IQR 56-180) after ALK (p=0.003). We conclude that after initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain low efficacy of ALK rechallenge.

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The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

Cancer Biomarkers ◽

10.3233/cbm-210349 ◽

2021 ◽

pp. 1-11

Author(s):

Deniz Can Guven ◽

Oktay Halit Aktepe ◽

Melek Seren Aksun ◽

Taha Koray Sahin ◽

Gozde Kavgaci ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Multivariate Analyses ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Free Survival ◽

Patients With Cancer ◽

Early Progression ◽

Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

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