Aggressive Pituitary Macroadenoma Treated With Capecitabine and Temozolomide Chemotherapy Combination in a Patient With Nelson's Syndrome: A Case Report.
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ABSTRACT:
SUBMITTER: Mirallas O
PROVIDER: S-EPMC8632214 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long-acting pasireotide and bromocriptine provided biochemical control of growth hormone and prolactin in a patient with plurihormonal pituitary macroadenoma, allowing near-complete tumor excision while restoring pituitary function and avoiding adjunctive radiotherapy. Pasireotide initiation resulted in hyperglycemia, which stabilized after a few months and resolved upon pasireotide discontinuation (ACCESS; NCT01995734).
| S-EPMC6406151 | biostudies-literature
Project description:IntroductionAggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.MethodsThis was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150-200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.ResultsThe study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6-14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.ConclusionEarly initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.
| S-EPMC8718901 | biostudies-literature
Project description:BackgroundThe endoscopic transsphenoidal approach is an efficient minimally invasive procedure for removal of pituitary tumors that can be accomplished through a one-hand or two-hand approach. The one-hand procedure through one nostril is more intuitive for surgeons, but maneuvering the instruments can be restrictive. The two-hand procedure using a one-and-half nostril approach provides more precise manipulation. This study aimed to compare the surgical outcomes of one-hand/mono-nostril and two-hand/one-and-half nostril surgeries for resection of large pituitary tumors by a single neurosurgeon.Materials and methodsThe surgical data of 78 consecutive cases with pituitary macroadenoma (diameter >1 cm) were reviewed retrospectively. Altogether, 30 cases received one-hand/mono-nostril surgery, while 48 cases received two-hand/one-and-half nostril surgery. Postoperative outcomes of the two operations were compared.ResultsThe operative time, hospital stay, residual rate of pituitary macroadenoma, visual field, surgical complications, and re-operative rates were slightly improved in the two-hand/one-and-half nostril surgery group compared with that in the one-hand/mono-nostril surgery group (all p>0.05). However, postoperative hypopituitarism was less frequent (1/48; 2.0%) with the two-hand/one-and-half nostril approach than with the mono-nostril approach (p = 0.004). Similar surgical outcomes were found in all patients with either small or large pituitary tumors, except that the difference in postoperative improvement in visual field change reached statistical significance (p = 0.044).ConclusionA single-surgeon endoscopic endonasal transsphenoidal surgery with two-hand/one-and-half nostril approach is an effective and safe procedure for removal of large pituitary tumors.
| S-EPMC8345891 | biostudies-literature
Project description:PurposeThis study aimed to evaluate the efficacy of radiation therapy (RT) for recurrent or residual pituitary macroadenoma (PMA) invading extrasellar regions.Materials and methodsPatients from 2000 to 2020 who received RT with conventional fractionation for recurrent or residual PMA were included. The patients were divided according to the type of tumor [functioning (fx) or non-fx] and the aim of RT (salvage RT alone, immediate postoperative RT, delayed postoperative RT). Local and biochemical failure-free rates (FFR) were calculated using the Kaplan-Meier method.ResultsWith a median follow up of 82 months (IQR; 42-132 months), 36 patients treated with conventional RT (total 45-54 Gy in 1.8 or 2 Gy per fraction) for recurrent or residual PMA were analyzed. The 10-year local FFRs after RT for non-fx and fx tumor were 100% and 74.4%, respectively (p=0.047). In the immediate postoperative RT group, the 10-year local FFR was 100%, which was higher than the 90% FFR for salvage RT alone or 80% FFR for the delayed postoperative RT group (overall p=0.043, immediate vs. salvage; p=0.312, immediate vs. delayed; p=0.072). The local FFR was compared according to size of tumor with a cut-off value of 4 cm, and there was no significant difference (10-year local FFR 100% vs. 84.7% for >4 cm vs. <4 cm, p=0.320). The extents of extrasellar region invasion were not predictive of local failure after RT. We found no grade ≥3 acute toxicities or newly developed visual impairments as a late toxicity of RT.ConclusionConventional RT is safe and effective for the local control of recurrent or residual PMA. Our data suggest that immediate postoperative RT can be beneficial in recurrent or residual PMA, although further studies to evaluate risk factors of treatment failure in terms of treatment and disease characteristics are required.
| S-EPMC9760886 | biostudies-literature
Project description:A 68-year-old woman was referred to our hospital with increased levels of biliary enzymes. On imaging, the patient was diagnosed with unresectable intrahepatic biliary tract cancer (BTC) with invasion of the portal vein and para-aortic lymph node metastasis (cT3N1M1, cStage IVb) and underwent endoscopic biliary drainage for the biliary stricture prior to therapy. The patient was subsequently enrolled in a phase III randomized trial (UMIN000014371/NCT02182778) and randomly assigned to receive gemcitabine/cisplatin/S-1 (GCS) combination therapy intravenously at doses of 1,000 or 25 mg/m2 on day 1 and orally twice daily at a dose of 80 mg/m2 on days 1-7 every 2 weeks. After 12 cycles of scheduled therapy without uncontrollable adverse effects, the patient achieved a good partial response with chemotherapy. Computed tomography (CT) revealed a marked reduction of the primary and metastatic lesions. In addition,18F-fluorodeoxyglucose-positron emission tomography/CT revealed diminishing abnormal uptake and no macroscopic evidence of factors adversely affecting tumor resectability. Therefore, the patient underwent extended right hepatic lobectomy, lymph node dissection and left hepaticojejunostomy. Finally, histological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. We herein present the case of a patient with intrahepatic BTC who achieved a pathologically complete response following combination chemotherapy with GCS.
| S-EPMC5228213 | biostudies-literature
Project description:We evaluated the efficacy of temozolomide (TMZ) or lomustine (CCNU) in combination with 6-thioguanine, capecitabine, and celecoxib for the treatment of recurrent high-grade glioma. Forty-three patients with recurrent glioblastoma and 31 patients with recurrent anaplastic glioma (AG) were enrolled in this open-label, non-comparative study. Patients previously treated with TMZ received CCNU while all others received TMZ; all patients received 6-thioguanine, capecitabine, and celecoxib. Endpoints were 12-month progression-free survival (PFS) for patients with AG, 6-month PFS for patients with glioblastoma, duration of PFS, and MRI-based objective response rates. Results from the TMZ and CCNU treatment arms were combined in the final analysis because there was no statistically significant difference between them. Thirty-eight patients with glioblastoma were treated with the lomustine-based regimen, and five received the TMZ-based regimen. For the 43 glioblastoma patients, the objective response rate was 12 and 33% had stable disease; the 6-month PFS was 14% and median overall survival 32 weeks. For the 31 AG patients, the combined objective response rate was 26 and 42% had stable disease; the 12 month PFS was 44%. Treatment was reasonably well tolerated with hematological toxicity common and more frequent with CCNU than TMZ. The combination therapy with 6-thioguanine, capecitabine and celecoxib plus CCNU or TMZ does not appear to be more effective than other alkylating agent schedules for patients with recurrent glioblastoma. The combination, however, is promising for patients with recurrent high-grade AG.
| S-EPMC5557017 | biostudies-other
Project description:A small subset of pituitary adenomas grows despite maximal treatment with standard therapies; namely, surgery and radiotherapy. These aggressive tumors demonstrate 2 patterns of growth: they may be locally aggressive or metastasize distantly, either hematogenously or through the spinal fluid. Further surgery and radiotherapy may be helpful for palliation of symptoms, but they are rarely definitive in the management of these malignant tumors. The only chemotherapy with established activity in the treatment of pituitary tumors is the alkylating agent temozolomide. At most, 50% of patients exhibit an objective response to temozolomide and the median time to progression is short; thus, there remains a significant unmet need for effective treatments within this patient population. Several targeted agents have reported activity in this tumor type-including small molecule inhibitors, checkpoint inhibitors, and other biologics-but remain investigational at this time.
| S-EPMC7566322 | biostudies-literature
Project description:In case of primary hypothyroidism, reactive pituitary hyperplasia can manifest as pituitary (pseudo) macroadenoma. We report the case of a 12-year-old boy who was evaluated for impaired growth velocity and increased body weight. Because of low insulin-like growth factor 1 levels and poor response to the growth hormone stimulation test, brain magnetic resonance imaging was performed and a pituitary macroadenoma was found. Treatment with levothyroxine was started, and thyroid function was evaluated approximately every 40 days to titrate the dosage. After few months of therapy, the size of the macroadenoma decreased and growth hormone secretion normalized. The pituitary returned to normal size in approximately 5 years. The boy went through puberty spontaneously and reached a normal adult height. In a patient affected by primary hypothyroidism, reactive pituitary hyperplasia can cause growth hormone deficiency; however, growth hormone secretion usually normalizes after starting levothyroxine treatment. Pituitary macroadenoma can be difficult to distinguish from severe pituitary hyperplasia; however, pituitary macroadenomas are rare in childhood, and our clinical case underlines how the hormonal evaluation is essential to achieve a correct diagnosis and prevent unnecessary surgery in a context of pituitary mass.
| S-EPMC8382546 | biostudies-literature
Project description:Poly-ADP ribose polymerase (PARP) inhibitors are constantly increasing in their indications for use as anti-cancer treatment in various neoplasms, the majority of which are linked with BRCA deficiency. Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting "BRCAness" or homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. With the current report we present the case of a heavily pretreated 55-year-old male patient diagnosed with stage IV ATM-deficient CRC, who was effectively treated with an off-label olaparib-irinotecan combination after exhaustion of all available treatment choices; furthermore, we discuss the existing data providing evidence for the use of PARP inhibitors in ATM-deficient CRC and encourage the implementation of next-generation sequencing (NGS) in patients with no other available treatment options.
| S-EPMC8728007 | biostudies-literature
Project description:ObjectivePituitary adenomas frequently extend into the suprasellar space. After a suprasellar tumor is removed, the superiorly extended arachnoid becomes redundant and sinks down into the intrasellar space which often hiders visualization and accessibility to the hidden space behind the evaginated arachnoid. We introduced arachnoid remodeling by clipping technique, and evaluated its usefulness and safety during TSS.MethodsTotal 223 patients who underwent arachnoid remodeling with our new clipping technique were included. Redundant arachnoid was clipped along the dural edge with multiple 2.6-mm titanium clips until the redundant arachnoid membrane no longer blocked the surgical route. To check for possible deterioration of hormonal function by this technique, we assessed anterior pituitary function of 166 patients who underwent arachnoid remodeling by clipping and compared this with those of other 429 control patients.ResultsOur technique greatly enhanced the accessibility and visualization of intrasellar and parasellar spaces, both of which are generally hindered by redundant arachnoid during transsphenoidal surgery (TSS). We found no difference in anterior pituitary function between a clip-assisted arachnoid remodeling group and the control group, implying that this technique does not result in hypopituitarism.ConclusionDuring TSS for pituitary adenomas with suprasellar extension, arachnoid remodeling by clipping technique is very useful and convenient for the management of the redundant arachnoid membrane to enhance visualization and surgical accessibility.
| S-EPMC9271807 | biostudies-literature