METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.
RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.
CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
MATERIALS AND METHODS: Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed.
RESULTS: Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed.
CONCLUSIONS: CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis.
METHODS AND MATERIALS: Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course.
RESULTS: A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively.
CONCLUSIONS: The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.
METHODS: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.
RESULTS: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.
CONCLUSION: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.
PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.
RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.
CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.
Case presentation: A 68-year-old gentleman of Malay ethnicity presented with left sided weakness associated with reduced sensation for one month. The patient was healthy and denied any constitutional symptoms, joint pains, rash or seizures. There was no recent trauma. Physical examination revealed left upper and lower limb motor grade power of 3/5 with upper motor neurone weakness of the left facial nerve. He had brisk reflexes and an upgoing extensor plantar response. Brain imaging (Magnetic Resonance Imaging) showed two lesions: one occupying the right head of the caudate nucleus and the other seen at the right side of the body of the corpus callosum. Histomorphology and immunohistochemistry confirmed Diffuse Large B-Cell Lymphoma (DLBCL) of non-germinal center type. He was treated with De Angelis protocol which involves chemoradiotherapy consisting of high dose methotrexate and whole brain radiotherapy (WBRT), followed by high dose cytarabine. Brain imaging post chemoradiation showed complete remission.
Conclusion: Prompt detection with appropriate therapeutic protocol could significantly minimise the permanent neurological deficits in patients with this rare and challenging lymphoid malignancy.
MATERIALS AND METHODS: A cohort of 60 patients with FIGO stage IB2-IVA cervical cancer who were treated with definitive concurrent chemoradiotherapy with cisplatin followed by intracavitary brachytherapy or external beam radiotherapy (EBRT) boost between November 2001 and May 2008 were analysed. Patients were initially treated with weekly intravenous cisplatin (40 mg/m2) concurrent with daily EBRT to pelvis of 45-50 Gy followed by low dose rate brachytherapy or EBRT boost to tumour. Local control rate, progression free survival, overall survival and treatment related toxicities graded by the RTOG criteria were evaluated.
RESULTS: The mean age was 56. At the median follow-up of 72 months, the estimated 5-year progression-free survival (PFS) (median PFS 39 months) and the 5-year overall survival (OS) (median OS 51 months) were 48% and 50% respectively. The 5-year local control rate was 67.3%. Grade 3-4 late gastrointestinal and genitourinary toxicity occurred in 9.3% of patients.
CONCLUSIONS: The 5-year PFS and the 5-year OS in this cohort were lower than in other institutions. More advanced stage at presentation, longer overall treatment time (OTT) of more than fifty-six days and lower total dose to point A were the potential factors contributing to a lower survival.
PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129).
RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.
CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
METHODOLOGY: In this open labelled randomized clinical trial, 40 participants aged between 18 and 65 with head and neck cancer who completed chemotherapy and/or radiotherapy in Hospital USM, Kelantan Malaysia or Hospital Taiping were recruited and randomized into two groups: Tualang honey (experimental) group or Vitamin C (control) group. They were prescribed with either daily oral Tualang honey 20mg or vitamin C tablet 100 mg for 8 weeks. Level of fatigue and quality of life were measured using FACIT-Fatigue and FACT H&N questionnaires at baseline, 4 weeks and 8 weeks. The white cell count and C-reactive protein level were also measured at baseline, 4 weeks and 8 weeks.
RESULTS: After four and eight weeks of treatment with Tualang honey or Vitamin C, the fatigue level for experimental group was better than in the control group, and the differences were statistically significant (p<0.05). Statistically significant improvements were seen on quality of life (p<0.05) for the experimental group at week 8, however, no significant improvements were seen in white cell count and C-reactive protein level between control and experimental group.
CONCLUSION: Our research provided support for the use of Tualang honey to improve CRF and QOL in head and neck cancer patients post chemotherapy or radiotherapy.
METHODS: Surgeons in the APFCP completed an Institutional Review Board-approved anonymous e-survey and/or printed letters (for China) containing 19 questions regarding nonsurgical close observation in patients who achieved clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT).
RESULTS: Of the 417 responses, 80.8% (n = 337) supported the W&W approach and 65.5% (n = 273) treated patients who achieved cCR after nCRT. Importantly, 78% of participants (n = 326) preferred a selective W&W approach in patients with old age and medical comorbidities who achieved cCR. In regard to restaging methods after nCRT, the majority of respondents based their decision to use W&W on a combination of magnetic resonance imaging results (94.5%, n = 394) with other test results. For interval between nCRT completion and tumor response assessment, most participants used 8 weeks (n = 154, 36.9%), followed by 6 weeks (n = 127, 30.5%) and 4 weeks (n = 102, 24.5%). In response to the question of how often responders followed-up after W&W, the predominant period was every 3 months (209 participants, 50.1%) followed by every 2 months (75 participants, 18.0%). If local regrowth was found during follow-up, most participants (79.9%, n = 333) recommended radical surgery as an initial management.
CONCLUSION: The W&W approach is supported by 80% of Asia-Pacific surgeons and is practiced at 65%, although heterogeneous hospital or society protocols are also observed. These results inform oncologists of future clinical study participation.