Long-term treatment outcomes of pediatric low-grade gliomas treated at a university-based hospital.

PURPOSE: A multimodality approach is generally considered for pediatric low-grade gliomas (LGG); however, the optimal management remains uncertain. The objective of the study was to evaluate treatment outcomes of pediatric LGG, focusing on long-term survival and factors related to outcomes. METHODS: A retrospective review of 77 pediatric LGG cases treated at Ramathibodi Hospital, Thailand between 2000 and 2018 was performed. The inclusion criteria were all pediatric LGG cases aged ≤ 15 years. Diffuse intrinsic pontine gliomas and spinal cord tumors were excluded. RESULTS: The median follow-up time was 8.2 years (range, 0.6-19.7). The median age at diagnosis was 6.2 years (interquartile range, 3.6-11.4). Treatments modality included tumor surgery (93%), chemotherapy (40%), and radiation therapy (14%). The 10-year overall survival (OS) and 10-year progression-free survival were 94% and 59%, respectively, for the entire cohort. The 10-year OS was 100% in three subgroups of patients: pilocytic subtype, WHO grade 1 tumors, and recipient of gross total resection. After multivariable analysis, no tumor surgery had a significantly unfavorable influence on overall survival. CONCLUSIONS: With a multimodality approach, pediatric LGGs had excellent outcome. Gross total resection is the standard primary treatment. Chemotherapy is the alternative standard treatment in incomplete resection cases, unresectable patients, or patients with progressive disease. Radiation therapy should be reserved as a salvage treatment option because of late complications that usually affect patients' quality of life.

Long-term clinical outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy using the CyberKnife® robotic radiosurgery system for vestibular schwannoma.

AIM: The study aimed to evaluate the long-term clinical outcomes of patients with vestibular schwannoma (VS) treated with stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT) with frameless robotic whole-body radiosurgery system (CyberKnife® ). METHODS: This retrospective analysis of prospectively collected data included 123 consecutive patients with VS treated at the Radiosurgery center, Ramathibodi Hospital, Bangkok, Thailand. SRS was recommended for patients with unserviceable hearing and Koos grade I-III tumors, and HSRT for patients with serviceable hearing or Koos grade III-IV tumors. Between March 2009 and December 2015, 23 patients (19%) were treated with SRS, whereas 100 (81%) received HSRT. The commonly used regimen was 12 Gy in one fraction for SRS and 18 Gy in three fractions for HSRT. RESULTS: After a median follow-up of 72 months (range: 12-123 months), the 5-year and 8-year progression-free survival (PFS) rates for the whole cohort were 96% and 92%, respectively. The PFS was not significantly different between the SRS and HSRT groups (p = 0.23). Among 28 patients with serviceable hearing in the HSRT group, the 5-year and 8-year hearing preservation rates were 87% and 65%, respectively. The rate of nonauditory complications was 14%. Koos grade III/IV was a predictor of disease progression and was associated with nonauditory complications. CONCLUSION: SRS and HSRT with the CyberKnife® system provided excellent long-term tumor control with a low rate of nonauditory complications. HSRT may result in acceptable hearing preservation rates.

Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity.

BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.

Outcome of postoperative radiation therapy for pediatric intracranial ependymoma: a single-institution review.

PURPOSE: To report outcome of postoperative radiotherapy (RT) in both new and recurrent grade II and III intracranial ependymomas in children treated at Ramathibodi Hospital. MATERIALS AND METHODS: Between 2006 and 2017, 24 pediatric intracranial ependymomas treated with postoperative RT were retrospectively reviewed. The median age at diagnosis was 44.5 months (range, 4-165 months). There were 14 (58%) males. Fourteen (58%) patients had infratentorial tumor. The median maximal diameter of tumor at diagnosis was 4.45 cm (range, 2.2-10 cm). Fourteen (58%) patients had anaplastic tumor. Gross total resections were performed in 14 (58%) patients. The median prescribed dose was 54 Gy (range, 45-60 Gy). The median total treatment time was 43 days (range, 37-78 days). RESULTS: The median clinical follow-up time was 44.5 months (range, 1-146 months). There were nine recurrences, five of which occurred at the primary tumor site. The estimated 5-year progression-free survival rate was 56%. The estimated 5-year overall survival rate was 75%. Extent of resection was the only factor associated with improved progression-free survival and overall survival after univariate testing. Six from nine patients with recurrent diseases underwent further surgery or further RT. These six patients had better median overall survival than the three who did not. Acute complication was mostly transient and tolerable. No late radiation effect was found. CONCLUSIONS: Postoperative radiation is an effective treatment. GTR is associated with better PFS and OS. Aggressive salvage local treatments for recurrent patients can result in good overall survival. Longer follow-up is needed in account for late relapse.

Reported outcomes of children with newly diagnosed high-grade gliomas treated with nimotuzumab and irinotecan.

PURPOSE: The outcome of children with high-grade gliomas (HGGs) treated with radiation and adjuvant chemotherapy remains poor. The expression of epidermal growth factor receptor (EGFR) has been established in children with HGGs. This report demonstrated the outcomes of adjuvant nimotuzumab, an EGFR inhibitor, with irinotecan in pediatric HGGs. METHODS: Children with newly diagnosed HGGs were enrolled. Two weeks after surgery, nimotuzumab with a dose of 150 mg/m2 was given every week during radiation. After completion of radiation, a 4-week cycle of nimotuzumab (150 mg/m2) at week 1 and 3 and irinotecan (125 mg/m2) at week 1, 2, and 3 was given. RESULTS: Sixteen patients (5 females, 11 males), with a mean ± SD age of 8.2 ± 3.5 years were included. Tumors were located at the supratentorial region (50.0%), infratentorial region (43.8%), and both locations (6.2%). The 5-year PFS and OS were 19.9 ± 11.6 and 31.5 ± 13.0%, respectively. Median times of PFS and OS were 1.8 and 1.9 years, respectively. Prognostic factors related to good outcome were the location of tumor at the supratentorial region or outside brainstem and the extension of surgery. Side effects were minimal, with grade 1 anemia in three patients and diarrhea in one patient. Although, the adjuvant regimen of nimotuzumab and irinotecan slightly increases the overall outcome when compared to the historical study, the advantages of this protocol were minimal side effect, short period of hospitalization, and improved OS in patients who received extensive surgery.

DCE-MRI-Derived Parameters as Predictors of Response to Neo-Adjuvant Chemoradiation Treatment of Rectal Carcinoma.

BACKGROUND: Preoperative combined chemoradiation treatment (CRT) is now accepted as the treatment of choice due to its benefits of decreasing the primary tumor volume and enhancing the sphincter preservation surgery. Determining whether a patient is responding to therapy is crucial for rectal cancer patients who may benefit from prompt treatment modifications. OBJECTIVE: To evaluate the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the treatment response. MATERIAL AND METHOD: Nineteen patients with histologically proven rectal adenocarcinoma who were candidates for neo-adjuvant CRT were prospectively included. All patients were examined by conventional and DCE-MRi at three time points (pre-, during-, and post-CRT). Surgical resection was performed after complete CRT. The pathological response and Dworak regression grade were assessed. All parameters were blindly analyzed. RESULTS: The median pathologic response rate for all patients was 40%. Dworak regression grades of 0, 1, 2, 3, and 4 were found in 0.0%, 21.1%, 42.1%, 26.3%, and 10.5% of patients, respectively. The tumor thickness and length were 30% and 32.9% lower at during-CRT and 40.6% and 44.7% lower post-CRT and had moderate and fair negative correlations with the pathologic response rate and Dworak regression rate, respectively. Among the DCE-MRI parameters, only a change in the time to peak between pre- and during-CRT was correlated with the Dworak regression grade (p = 0.01). The percentage change in the time to peak in patients with poor regression (grades 0-1) was significantly greater than in patients with intermediate/complete regression (grades 2-4) [139.25% vs. 6.13%]. CONCLUSION: Changes in the tumor thickness and length evaluated by conventional MRI and the time to peak evaluated by DCE-MRI during CRT may be useful for predicting the treatment response of rectal cancer patients.

Effects of Radiation Therapy on Immunological and Virological Status in HIV-Infected Cancer Patients in Thailand: A Multicenter Prospective Study.

BACKGROUND: Radiation therapy (RT) is the core part of cancer multidisciplinary management which causes myelosuppression. The current standard or RT among HIV-positive cancer patients who are immuno-compromised does not differ from that of HIV-negative ones. OBJECTIVE: To determine the effects of radiation therapy on immunological and virological status among HIV-infected cancer patients. MATERIAL AND METHOD: A prospective observational study was conducted of HIV-infected cancer patients who received definitive RT in seven hospitals in Thailand. Blood samples were taken to determine immune status using CD4%, and virological status was identified using plasma HIV-RNA viral load (HIV-VL) assay: at baseline before RT at the last week of RT completion; and at the 6-month follow-up visit. Additional CD4% test was performed at the 3-month follow-up visit. RESULTS: Ninety HIV-infected cancer patients from seven hospitals in Thailand were included in the analysis. The median age was 40 years old (range 19-61). Seventy-six patients (84.4%) were female and 65 (72.2%) were cases of invasive cervical cancers. Eighty-seven percent of patients had been receiving antiretroviral treatment (ART) before RT The mean CD4% at baseline, RT completion, 3-month and 6-month follow-up visits, were 18.7%, 20.1%, 16.8% and 17.1%, respectively. The proportion of CD4% reduction in the non-ART group was higher than that of the ART group throughout the period, particularly at the 3-month follow-up visit (100% vs. 29.7%, p = 0.0004). Six cases had a HIV-VL increase of more than 10 times (1-log10) at completion of RT: 3 of these were non-ART and 3 were ART-uncontrolled viral suppression. CONCLUSION: RT had a suppressive effect on immunological status in HIV-infected cancer patients, particularly in the subacute period among those who were not on ART HIV-disease progression was observed during radiation treatment in HIV-infected cancer patients without ART and those with ART-uncontrolled viral suppression.

The Clinical Outcome of Hypofractionated Stereotactic Radiotherapy With CyberKnife Robotic Radiosurgery for Perioptic Pituitary Adenoma.

Stereotactic radiation technique including single fraction radiosurgery and conventional fractionated stereotactic radiotherapy is widely reported as an effective treatment of pituitary adenomas. Because of the restricted radiation tolerance dose of the optic pathway, single fraction radiosurgery has been accepted for small tumor located far away from the optic apparatus, while fractionated stereotactic radiotherapy may be suitable for larger tumor located close to the optic pathway. More recently, hypofractionated stereotactic radiotherapy has become an alternative treatment option that provides high rate of tumor control and visual preservation for the perioptic lesions within 2 to 3 mm of the optic pathway. The objective of the study was to analyze the clinical outcomes of perioptic pituitary adenomas treated with hypofractionated stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median tumor volume was 3.35 cm3 (range, 0.82-25.86 cm3). The median prescribed dose was 25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were smaller in size. No patient's vision deteriorated after hypofractionated stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13 patients. No newly developed hypopituitarism was detected in our study. These data confirmed that hypofractionated stereotactic radiotherapy achieved high rates of tumor control and visual preservation. Because of the shorter duration of treatment, it may be preferable to use hypofractionated stereotactic radiotherapy over fractionated stereotactic radiotherapy for selected pituitary adenomas immediately adjacent to the optic apparatus.

Long Term Outcomes of Preoperative versus Postoperative Concurrent Chemoradiation for Locally Advanced Rectal Cancer: Experience from Ramathibodi Medical School in Thailand.

OBJECTIVES: The study analyzed and compared the long term outcome in locally advanced rectal cancer treated with preoperative and postoperative concurrent chemoradiation (CCRT). MATERIALS AND METHODS: A retrospective review of 105 patients with stage T3-T4 or regional lymph node positive adenocarcinoma of rectum treated with preoperative or postoperative CCRT at Ramathibodi Hospital during 2005 to 2010 was performed. The results of treatment were reported with 5-year overall survival (OS), 5- year locoregional recurrence free survival (LRFS), and toxicity according to preoperative versus postoperative concurrent chemoradiation (CCRT) groups. RESULTS: Among 105 patients, 34 (32%) were treated with preoperative CCRT and 71 (68%) with postoperative CCRT. At the median follow-up time of 50.5 months (range 2-114 months), five-year OS and LRFS of all patients were 87% and 91.6%, respectively. The study found no difference in 5-year OS (81.7% vs 89.2 %) or LRFS (83.4% vs 95.1%) between preoperative versus postoperative CCRT. Seven cases of loco-regional recurrence were diagnosed, 4 (11.8%) after preoperative CCRT and 3 (4.2%) after postoperative CCRT. The recurrent sites were anastomosis in all patients. There was no significant factor associated with outcome after univariate and multivariate testing. Grade 3 or 4 acute and late complications were low in both preoperative and postoperative CCRT groups. CONCLUSIONS: Locally advanced rectum cancer patients experience good results with surgery and adjuvant concurrent chemoradiation.

Outcomes for Pituitary Adenoma Patients Treated with Linac- Based Stereotactic Radiosurgery and Radiotherapy: a Long Term Experience in Thailand.

BACKGROUND: The study analyzed the long term clinical outcomes of pituitary adenoma cases treated with the first Thailand installation of a dedicated Linac-based stereotactic radiation machine (X-Knife). MATERIALS AND METHODS: A retrospective review of 115 consecutive pituitary adenoma patients treated with X-Knife at the Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand from 1997 to 2003 was performed. Stereotactic radiosurgery (SRS) was selected for 21 patients (18%) including those with small tumors (≤3 cm) located ≥5 mm. from the optic apparatus, whereas the remaining 94 patients (82%) were treated with fractionated stereotactic radiotherapy (FSRT). RESULTS: With a median follow-up time of 62 months (range, 21-179), the six-year progression free survival was 95% (93% for SRS and 95% for FSRT). The overall hormone normalization at 3 and 5 years was 20% and 30%, respectively, with average time required for normalization of approximately 16 months for SRS and 20 months for FSRT. The incidence of new hypopituitarism was 10% in the SRS group and 9% in the FSRT group. Four patients (5%) developed optic neuropathy (1 in the SRS group and 3 in the FSRT group). CONCLUSIONS: Linac-based SRS and FSRT achieved similar high local control rates with few complications in pituitary adenoma cases. However, further well designed, randomized comparative studies between SRS versus FSRT particularly focusing on hormone normalization rates are required.

Clinical outcome of postoperative radiotherapy with or without chemotherapy in adult glioblastoma multiforme in Ramathibodi Hospital: a retrospective study.

OBJECTIVE: To identify the treatment outcome of glioblastoma multiforme (GBM) in Ramathibodi Hospital from overall survival rate and related prognostic factors. MATERIAL AND METHOD: Medical records of patients with histological diagnosis of GBM treated at Radiation Oncology Division, Radiology Department, Ramathibodi Hospital between 2000 and 2010 were reviewed and available data extracted for evaluation of treatment outcome. RESULTS: There were 47 patients with mean age at diagnosis of 51.9 years (range from 18 to 82 years). Surgery (partial 76.6%, total 12.8%, and biopsy 10.6%) followed by postoperative radiotherapy (mean dose 52 gray) was the treatment of choice with or without concurrent and adjuvant Temozolomide (TMZ). With median follow-up time of 0.9 years, the median survival of the patients was 2.1 years (95% CI 1.08-7.36), whereas one and two-year overall survival rates were 78.0% and 57.8%, respectively. In univariate analysis, persistent neurological deficit after surgery and presenting symptom of visual disturbance were identified to lower overall survival while multivariate analysis, younger age, and higher radiation dose were identified as favorable prognostic factors to improve overall survival. Re-surgery or re-irradiation in some selected cases of recurrent or progressive disease was considered as a choice for palliative treatment. CONCLUSION: Proper management of GBM patient was surgical removal and postoperative radiotherapy with or without chemotherapy. Proper palliative treatment modality was considered in selected cases of recurrent or progressive disease.

Preliminary experience of CyberKnife treatment of lung metastasis: the question about real clinical benefit.

OBJECTIVE: Evaluate the effectiveness of radiotherapy plan and physical parameters including local tumor response and clinical outcome of lung metastasis in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases with twenty lesions of lung metastasis patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was calculated approximately to biological equivalent dose (BED) around 60 to 100 gray (Gyz). The response of each lesion to treatment was evaluated from roentgenographic study during follow-up period along with adverse event, status of patients, and disease. RESULTS: At the third month after treatment, roentgenographic partial response (PR, 50% decrease in size) was demonstrated in eight lesions and stable disease (SD, unchanged size) in eight lesions with no complete response (CR, disappearance of tumor) detected. Progressive disease (PD, 25% increase in size) of six treated lesions was detected during the follow-up period. At the time of report, two patients were alive and still received palliative chemotherapy, two patients died from uncontrolled progressive metastases and failed palliative chemotherapy, and two patients lost follow-up after progressive metastases with unknown surviving status. No severe adverse event was observed. The treatment planning parameters demonstrated borderline of radiation dose homogeneity, and conformality coverage of the target volume. CONCLUSION: This preliminary report aimed to provide the idea of choosing the appropriate lung metastasis patient to receive CyberKnife treatment that must strictly clarify the real clinical benefit of each selected case to achieve the best outcome from this special treatment procedure.

Preliminary experience of CyberKnife treatment of primary non-small cell lung cancer.

OBJECTIVE: Provide the effectiveness of treatment protocol, radiotherapy plan, technique, and early clinical results of inoperable primary non-small cell lung cancer (NSCLC) in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases of inoperable primary NSCLC patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was 45 gray (Gy) in three consecutive fractions for peripherally located tumor and 50 Gy in five fractions within two weeks for centrally located tumor (biological equivalent dose, BED, 112.5 Gy 10, and 100 Gy 10, respectively). The response to treatment was evaluated from roentgenographic study during follow-up period along with clinical outcome and adverse event. RESULTS: Overall response after the treatment was demonstrated in five cases with roentgenographic complete response (CR, disappearance of tumor) and partial response (PR, 50% decrease in size) in two and three cases, respectively without any severe adverse event. The treatment planning parameters demonstrated the effectiveness of radiation dose homogeneity and conformity coverage of the target volume. CONCLUSION: This preliminary report has provided the effectiveness of treatment plan and local tumor controlled without severe adverse event for primary inoperable NSCLC patients receiving CyberKnife treatment.

In vivo whole body dosimetry measurement technique of total body irradiation: a 12-year retrospective study result from one institute in Thailand.

OBJECTIVE: The main problem of total body irradiation (TBI) is how to maintain radiation dose homogeneity throughout the body during a treatment course. The simple set up treatment with non-complicated in vivo dosimetry measurement technique is the ideal method to solve this problem. For this reason, the authors have reported the results of in vivo dosimetry measurement method to prove the reliability of dose distribution from the authors' TBI technique. MATERIAL AND METHOD: The authors reviewed the data of dose measurement record from 53 patients' treatment files to report the uniformity of absorbed in vivo dose distribution throughout the whole body from TBI with semiconductor detectors and ionization chamber with the accepted homogeneity within +/- 10% of the prescribed dose. The result was reported in the term of mean and standard deviation of absorbed dose difference from the prescribed dose. RESULTS: The uniformity of radiation dose distribution throughout the whole body of all patients calculated from semiconductors was accepted with mean difference value of -3.2 +/- 2.5% from the prescribed dose and the difference of mean absorbed dose value at midline point between semiconductor and ionization chamber was 4 +/- 3.3%. CONCLUSION: This TBI dosimetry measurement technique has been proved to exhibit the reliability of dose homogeneity throughout the whole body within the accepted value. This could be applied for use at any institute that has some limitation in resources and small treatment room.

Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function.

BACKGROUND: Amifostine has a potential role for salivary gland protection in head and neck cancer patients who had radiotherapy. MATERIAL AND METHOD: Sixty-seven head and neck cancer patients were randomized to receive radiotherapy or radiotherapy plus Amifostine. The efficacy of the treatment was determined by a questionnaire evaluating dryness of mouth and the oral comfort, the RTOG/EORTC acute/late radiation morbidity scoring criteria, collection of the whole saliva and the 99mTc-pertecnetate scintigraphy of the salivary glands. RESULTS: Amifostine significantly reduced the mean questionnaire scores from 6.49 to 3.73, the incidence of grade > or = 2 mucositis from 75% to 36% and acute xerostomia from 82% to 39%. The salivary gland function returned to normal at a rate of 36.3% in the Amifostine group versus 9.1% in the control group. CONCLUSION: Amifostine is effective in reducing the incidence and severity of acute mucositis, acute and late xerostomia in head and neck cancer patients.

Acute effects of postmastectomy radiotherapy after immediate TRAM flap reconstruction in breast cancer patients.

OBJECTIVES: To study the acute effects of radiotherapy after mastectomy and immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction in breast cancer patients treated at Ramathibodi Hospital. MATERIAL AND METHOD: Between January 2004 and March 2005, ten breast cancer patients (age 32-51 years) were treated with postoperative radiotherapy after mastectomy and immediate TRAM flap reconstruction. Medical records of these patients were retrospectively reviewed. Radiotherapy was delivered to the chest wall and reconstructed TRAM flap using 6-MV x-ray or Cobalt-60. The total dose was 45 to 50.4 Gy delivered in 25 to 28 fractions. Patients were evaluated weekly during the course of radiation and then at 1 and 2 months after treatment completion to determine acute effects or toxicities of radiation. RESULTS: During radiation, 3 patients developed erythema or mild hyperpigmentation of the skin, and 4 developed moderate hyperpigmentation. Three patients who were treated with Cobalt-60 and/or bolus to the chest wall developed skin desquamation (1 dry desquamation, 2 moist desquamation). No patient required a treatment break because of acute side effects. One patient who received chemotherapy after radiation developed recalled moist desquamation. CONCLUSION: Radiotherapy after mastectomy and immediate TRAM flap reconstruction is well tolerated and is not associated with increased acute complication or radiation interruption. The authors have noticed that chemotherapy given after radiation was related to severe skin reaction, so it should be used with caution.