Journal of Integrative Oncology

Purpose: Predictive marker of bevacizumab activity is an unmet medical need. Our objective was to evaluate the trough concentration of bevacizumab in patients with recurrent glioblastoma and to analyze its potential association with patient characteristics and outcome.
Methods: We retrospectively included patients with recurrent glioblastoma treated with bevacizumab and chemotherapy with available plasma collected before the second bevacizumab administration (residual time). Trough bevacizumab concentrations and antibodies against bevacizumab were quantified by enzyme linked immunosorbent assay (ELISA).
Results: We included 21 patients with a median age of 63.4 years at bevacizumab initiation. Occurrence of antibody against bevacizumab was not observed. Median pre-cycle 2 trough concentration of bevacizumab was 87.1 μg/mL (range, 21.7 μg/mL -151.8 μg/mL). Trough concentration of bevacizumab was not correlated to patient age (p=.529), gender (p=.622), weight (p=.403), size (p=.871), Body Mass Index (p=.439), Karnofsky Performans Status (p=.988) and steroid intake (p=0.403). No correlation was found between trough bevacizumab concentration and response rate (p=.856). The highest tertile of trough bevacizumab concentration tended to be associated with poor progression-free survival (p=0.152), while no correlation was observed for overall survival.
Conclusion: Evaluation of the trough concentration of bevacizumab during treatment for patients with glioblastoma is feasible and highly variable. Its prognostic value

The integration of PET and CT scans allows the simultaneous use of biologic and anatomic imaging data for better delineating tumor and sparing normal critical structures. The aim of this study is to assess the impact on target volume delineation using CT vs. PETCT based plans, and to determine radiobiological effect on tumor and normal tissue by comparing Tumor control probability (TCP) & normal tissue complication probability (NTCP) of CT & PET-CT based plans. 15 patients of inoperable NSCLC planned for radical radiotherapy, underwent a planning CT scan of the thorax. Target volumes were contoured. Later PETCT images with the auto contoured MTV (Metabolic target volume) images, were fused with the planning CT images. Margins were similarly given to PETMTV for the generation of PET CTV and PET PTV. 3 Dimensional conformal radiotherapy (3DCRT) plans were made on the planning CT images and the planning PETCT images, and were compared dosimetrically and radio biologically. The study shows that the use of PETCT resulted in significant decrease in PETCT generated MTV versus GTV delineated on CT. Also, there was statistical significant decrease in the volume of the normal lung irradiated in terms of V40 and the MLD. TCP for PETCT based plans was significantly higher than that with CT based plans. Also, PETCT based planning resulted in a statistically significant decrease in the NTCP for lung and spinal cord. Therefore, the study concludes that incorporation of PETCT into radiotherapy planning of NSCLC is technically feasible and dosimetrically appealing strategy for patient treatment.

A 35 year old male presented with pain in right middle finger since 5 y associated with shortening of right middle finger since 3 y. He had dull aching pain and blackish discoloration of the finger since 5 y. Examination revealed painful, restricted movements at inter-phalangeal joint and shortening of the finger of about 4 cm. After a thorough work up of the patient, he was diagnosed to have Gorham’s disease of the third metacarpal which was confirmed by histopathology reports. The patient was managed by surgical reconstruction to provide a functional and cosmetically acceptable hand.

Study background: Glioblastoma (GBM) is the most common subtype of primary brain tumor in adults. The aim was to evaluate the impact of biofield treatment potential on human GBM and non-GBM brain cells using two time-lapse video microscopy technique.
Methods: The human brain tumor, GBM cultured cells were divided into two groups viz. GBM control and GBM treatment. Similarly, human normal brain cultured cells (non-GBM) were taken and divided into two groups viz. non- GBM control and non-GBM treatment. The GBM and non-GBM treatment groups were given Mr. Trivedi’s biofield treatment for the assessment of its potential. Two time-lapse (10 hours prior; 10 hours after) video microscopy experiment was performed on tumor and non-tumor brain cells in six replicate (n=6). For each microscopic field, the total cell number was counted and each cell was tracked over the 20 hours period. The potential impact of biofield treatment was assessed by comparing cell death rate in both GBM and non-GBM cells before and after biofield treatment.
Results: GBM control cells showed a basal level of cell death 10 hours prior and 10 hours after the biofield treatment, and the rate remained unchanged over the 20 hours period, while in treatment group of GBM, cell death rate was exponentially increased (41%) after biofield treatment as compared to control. The treated non-GBM cultured cells showed a significant reduction (64%) of cell death rate i.e. protective effects as compared to non-GBM control.
Conclusion: Altogether, data suggests that biofield treatment has significantly increased the cell death rate of treated GBM cells and simultaneously boost the viability of normal brain cells. Therefore, biofield treatment could be a suitable alternate treatment strategy for cancer patients in near future.

Background: The evaluation of active hexose correlated compound (AHCC) on hepatic metabolism mediateddrug interaction is critical in current clinical setting as there is little published information on the potential effect on drug efficacy and safety. The primary objective of this study was to evaluate the potential phase II hepatic metabolism pathways associated with the metabolism of AHCC and to determine potential drug/AHCC interactions.
Methods: Four primary hepatic metabolism phase II pathways were evaluated: glutathione S-transferase (GST), quinone oxidoreductase (QOR), catechol-O-methyltransferases (COMT) and uridine diphosphate (UDP)- glucuronosyltransferase (UGT). Pooled human liver microsomes and human liver S9 fractions were utilized to evaluate QOR and UGT metabolism inhibition assays. The pool human liver S9 fractions were used to assess GST activity. Cryopreserved inducible human liver hepatocytes were used to evaluate potential induction of UGT and COMT metabolism. All experiments were carried out in triplicate.
Results: Data demonstrated that AHCC is not an inhibitor of GST or UGT pathways, but may be a potential inhibitor of QOR pathway. Evaluation of induction of the phase II pathways demonstrated that AHCC showed potential induction of the UGT 1A3 and 1A6 pathways. There was no induction of the COMT pathway.
Conclusion: Historically, drug interaction studies have only focused on Phase I metabolism pathways, so currently there is very limited information regarding the phase II metabolism of most commonly used medications. In conclusion, additional studies are warranted to determine potential of any phase II hepatic interactions with AHCC when administered with other medications or supplement that are substrates of these pathways.

Non-Hodgkin Lymphoma (NHL) is a frequent cancer in elderly population. Comorbidities often influence the choice among different treatment options; particularly, concern about anthracyclines’ cardiotoxicity induces to select less effective chemotherapy regimens. The present retrospective study includes NHL patients treated in a single institution with and without antracyclines; clinical results have been analysed comparing both elderly (> 70 years) and not-elderly and impaired and not impaired population. 68 patients affected by NHL, diagnosed between 1996 and 2011, have been included. Median OS of whole population was 34 months; there was no significative difference in OS related to age or comorbidities among patients treated with anthracyclines-based regimens. Median OS of elderly patients not treated with anthracyclines resulted significantly lower, irrespectively of comorbidities (20 months); 94% of elderly patients who undergone anthracyclines-based regimen reported symptoms relief and performance status improvement, compared to 75% of elderly not treated with anthracyclines. Results of this retrospective analysis suggest that anthracyclines-based chemotherapy produces a significant improvement in OS and QoL,even in elderly or impaired patients. Comorbidities and age don’t seem absolute contraindications to anthracycline-based chemotherapy.

Background: primary central nervous Hodgkin Lymphoma is a very rare event that occurs in less than 0.2% of cases, most of them in immunosuppressed patients.
Case presentation: We describe a 59 year-old man with a 20 year history of ulcerative colitis treated with azathioprine during 6 years who developed a primary central nervous system Hodgkin Lymphoma. Inmunohistochemical study was positive for Epstein-Barr virus showing a type II latency pattern. The patient was treated with chemotherapy regimen consisting on high dose methotrexate and cytosine arabinoside achieving complete remission that remains more than five years after diagnosis.
Conclusions: To the best of our knowledge we present the first case in the literature of a primary central nervous system hodgkin lymphoma in a immunossupressed patient due to azathioprine with a long remission after chemotherapy alone.

Background: microRNA-22 (miR-22) was frequently altered in numerous cancers and was involved in various cellular processes related to carcinogenesis. However, the role of miR-22 in cervical cancer haven’t been investigated.
Methods: 62 pairs of fresh cervical cancer tissue were collected between May 2012 and March 2015. Real-time quantitative RT-PCR assay was performed to evaluate the expression levels of miR-22. The survival curves were determined using the Kaplan-Meier method and Cox regression for statistics. The roles of miR-22 in cell proliferation, migration and invasion were identified using miR-22 mimic-transfected cells. In addition, the regulatory effect of miR- 22 on suppressor of cancer cell invasion (SCAI) was evaluated using qRT-PCR a dual luciferase reporter assay.
Results: miR-22 expression in cervical cancer tissues was significantly lower than that in normal tissues (mean ± SD: 1.944 ± 1.026 vs. 4.981 ± 1.507, P < 0.0001). Low miR-22 expression level was correlated with FIGO stage (P = 0.00004), tumor differentiation (P = 0.0002), and lymph-node-metastasis stage (P = 0.0099). Kaplan-Meier analysis with the log-rank test indicated that low miR-22 expression had a significant impact on overall survival (P = 0.0016) and progression-free survival (P = 0.0005). Moreover, ectopic miR-22 expression potently inhibited cervical cancer cell growth (P < 0.01), migration (P < 0.01) and invasion (P < 0.01) in vitro. miR-22 overexpression in cervical cancer cell lines decreased MMP1 and MAPK1 expression at the translational level and reduced MMP1/MAPK1- driven luciferase-reporter activity (P < 0.01).
Conclusions: Our data demonstrated that the expression of miR-22 was downregulated in cervical cancer, and associated with overall survival as well as progression-free survival, suggesting that miR-22 could serve as an efficient prognostic factor for cervical cancer patients.

In the last decades, survivorship of metastatic patients increased so much that orthopaedic surgeons have to perform a long lasting local treatment of bone secondary lesions to improve quality of life. The treatment has to be personalized for each patient according to tumour prognosis mainly due to histology or solitary/multiple metastases, metastatic localization, patient general conditions, previous normal or pathological ambulation. In the secondary lower limb lesions, when general conditions and prognosis are good, surgeons have to be aggressive, performing resections and implanting prostheses to allow a quick rehabilitation program. Otherwise, they can perform a more conservative surgery by curettage and local adjuvants in metastatic lower and upper limb lesions, with prognosis and general conditions are poor. Local treatment of bone metastases with adjuvants has been widely described in literature. The purpose of this review is to consider studies on antiblastic loaded acrylic cement as a treatment option for selected tumors.

Purpose: Nasopharyngeal carcinoma (NPC) has the worldwide highest incidence in Southern China. Here, we investigate the efficacy and safety of induction chemotherapy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus concurrent cisplatin based intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC.

Materials and Methods: From October 2009 to August 2012, 76 NPC patients treated by TFP induction chemotherapy plus concurrent cisplatin-IMRT were retrospectively recruited. The survival rate, accurate and late toxicities were further analyzed with 3 year follow-up.

Results: The median follow-up time was 42 months (range, 8 to 60 months). The 3- year disease free survival (DFS), overall survival (OS), Local relapse free survival (LRFS), Distant metastasis free survival (DMFS) was 86.6%, 94.5%, 94.7%, and 89.2%, respectively. The major acute toxicities were myelosuppression, gastrointestinal disorders, and mucositis. The major late toxicities were skin reaction, xerostomia and hearing loss. Multivariate analyses indicated that lymph node metastasis status (N stage) was independent prognostic factor for DFS (P = 0.044, hazard ratio 4.832) and DMFS (P = 0.036, hazard ratio 7.309).

Conclusions: TPF induction chemotherapy plus concurrent cisplatin-IMRT achieved satisfying 3-year survival rates with acceptable toxicities, suggesting that this combined therapeutic regimen might be effective for locoregionally advanced NPC.