Background The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the ...pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population. Methods We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables. Results 260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009). Conclusions Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes. Keywords: Neoadjuvant treatment, HER2+, Early breast cancer, Pertuzumab, HER2 dual blockade, Real world data
Trastuzumab-related cardiotoxicity has been reported in patients receiving trastuzumab concurrently with other agents, especially with anthracyclines. Cardiac function damage is generally rare, ...precox and mild with trastuzumab alone.
We report the case of a 49 year-old woman affected by metastatic breast cancer who developed trastuzumab-related cardiogenic shock due to pump failure (with LVEF of about 15%) after three months of treatment. After a long hospitalization in the cardiac intensive care unit and a proper treatment, LVEF increased to 50% and, due to a severe progression of disease, trastuzumab was resumed and continued for more than one year.
This is a case of particularly severe cardiotoxicity related to trastuzumab treatment, which was recovered with pharmacological treatment and the temporary discontinuation of the treatment. Trastuzumab was safely resumed after clinical and echocardiographic parameters improvement.
Primary cardiac angiosarcoma is extremely aggressive; however, it is often misdiagnosed because of its rarity. For locally advanced tumors, doxorubicin-based chemotherapy regimens are the standard of ...treatment, even if the gain in term of progression-free survival is limited and is no longer than 5 months.
We report the case of a Caucasian 23-year-old man with locally advanced cardiac angiosarcoma who underwent radical surgical resection after a prolonged response to weekly docetaxel and complementary radiotherapy.
Combined treatment with weekly docetaxel and radiotherapy may be a valid alternative for the treatment of locally advanced cardiac angiosarcoma; the combination can lead to radical surgical resections, avoiding the cumulative cardiotoxicity of antracycline-based regimens.
Glioblastoma is the most frequent malignant brain tumor and is characterized by poor prognosis, increased invasiveness, and high recurrence rates. Standard treatment for glioblastoma includes maximal ...safe surgical resection, radiation, and chemotherapy with temozolomide. Despite treatment advances, only 15-20% of glioblastoma patients survive to 5 years, and no therapies have demonstrated a durable survival benefit in recurrent disease. In the last 10 years, significant advances in knowledge of the biology and molecular pathology of the malignancy have opened the way to new treatment options. Clinical management of patients (pseudo-progressions, side effects of therapies, best supportive care, centralization in expertise care centers) has improved. In brain tumors, such as in other solid tumors, we have entered an era of immune-oncology. Immunotherapy seems to have an acceptable safety and tolerability profile in the recurrent setting and is under investigation in clinical trials in newly diagnosed glioblastoma patients. This review focuses on novel targeted therapies recently developed for the management of newly diagnosed and recurrent glioblastomas.
Almost all patients affected by glioblastoma experience recurrence of the disease.
Management of recurrent glioblastoma is a clinical challenge, and several elements should be taken into ...consideration when making treatment choice. Loco-regional treatments may be the best treatment approach in selected cases while systemic therapies or supportive care alone are necessary for other patients. Unfortunately, few drugs have shown clinical in this setting. This lack of effective treatments has made recurrent glioblastoma a disease orphan of an effective approach.
Results of recent clinical trials offer interesting perspectives and may controvert this axiom.
Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms ...(1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour.
We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS).
The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio HR = 0.342, 95% confidence interval CI: 0.221–0.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290–0.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375–3.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156–0.641, P = 0.001).
In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients.
•Grade II/III gliomas are classified in accordance with IDH mutation and 1p/19q deletion.•The role of grading as an independent prognostic factor remains matter of debate.•In our study, histological grade affects survival in IDH-mut grade II and III gliomas.•The impact of grade on survival is independent from clinical and molecular factors.
Background
Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on ...3rd line therapy or clinical trials specifically designed for this setting.
Methods
We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma.
Results
Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011).
Conclusions
Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.
Purpose:
Medulloblastoma is a rare tumor in adults and the use of adjuvant chemotherapy in average risk patients is debated.
Methods:
Patients included in our study were ⩾16 years of age, had ...histologically confirmed medulloblastoma, and underwent adjuvant radiotherapy with or without chemotherapy. Average risk was defined according to the Chang classification.
Results:
We included 48 average-risk patients. Median follow-up was 151.5 months (95% confidence interval, 124.5–178.5). Both progression-free survival (PFS) and overall survival (OS) were significantly influenced by adjuvant chemotherapy (PFS: hazard ratio HR, 0.334, p = 0.05; OS: HR, 0.187, p = 0.017) and by receiving the treatment in a referral center (PFS: HR, 0.250, p = 0.008; OS: HR, 0.295, p = 0.038).
Conclusions:
Treating patients with average-risk medulloblastoma in a referral center improves both PFS and OS, does adding adjuvant chemotherapy.
Background
Patients with low‐grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutation (mut) and 1p19q codeletion (codel) have a median overall survival of longer than 10 years. The aim of ...this study is to assess the role of postsurgical treatments.
Subjects, Materials, and Methods
We evaluated patients with LGGs with IDH mut and 1p19q codel; IDH1/2 was performed by immunohistochemistry and quantitative polymerase chain reaction. In all wild‐type cases, we performed next‐generation sequencing. 1p19 codel analysis was performed by fluorescence in situ hybridization.
Results
Among the 679 patients, 93 with LGGs with IDH mutation and 1p19q codel were included. Median follow‐up (FU) was 96.1 months. Eighty‐four patients (90.3%) were high risk according to Radiation Therapy Oncology Group criteria. After surgery, 50 patients (53.7%) received only FU, 17 (18.3%) chemotherapy (CT), and 26 (30.1%) radiotherapy (RT) with (RT + CT, 8 patients, 8.6%) or without (RT, 18 patients, 19.4%) chemotherapy. Median progression‐free survival (mPFS) was 46.3 months, 50.8 months, 103.6 months, and 120.2 months in patients with FU alone, with CT alone, with RT alone, or with RT + CT, respectively. Median PFS was significantly longer in patients who received postsurgical treatment (79.5 months, 95% confidence interval CI: 66.4–92.7) than patients who received FU (46.3 months, 95% CI: 36.0–56.5). Moreover, mPFS was longer in patients who received RT (alone or in combination with CT, n = 26, 113.8 months, 95% CI: 57.2–170.5) than those who did not (n = 67, 47.3 months, 95% CI: 36.4–58.2). In particular, temozolomide alone did not improve PFS with respect to FU.
Conclusion
RT with or without chemotherapy, but not temozolomide alone, could extend PFS in IDH mut 1p19q codel LGGs.
Implications for Practice
Low‐grade gliomas with high‐risk features, defined according to Radiation Therapy Oncology Group criteria, receive radiotherapy and/or chemotherapy as postsurgical treatments. Radiotherapy, however, has serious long‐term effects (cognitive impairment), which are to be taken into account in these young patients. Moreover, low‐grade gliomas with isocitrate dehydrogenase mutation and 1p19q codeletion (oligodendrogliomas) have an extremely long survival and a better prognosis. This study suggests that postsurgical treatments prolong the time before tumor progression in patients with good prognosis as well as those with oligodendroglioma. Moreover, temozolomide alone might not be effective in prolonging progression‐free survival.
Low‐grade gliomas with high‐risk features receive radiotherapy and/or chemotherapy as post‐surgical treatments. This article assesses the role of post‐surgical treatments for patients with low‐grade gliomas with isocitrate dehydrogenase mutation and 1p19q codeletion.
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