The main goal of treatment of soft-tissue sarcomas is achieving wide negative margins to improve local control and prevent recurrence. The role of radiation therapy (RT) is well established in ...sarcomas of the extremities; however, its role in unplanned surgery of soft-tissue sarcoma (when a mass presumed to be benign is resected and the pathology comes back as sarcoma, usually referred to as an “oops” operation) is inconclusive. This article reports on the effect of RT after an unplanned surgery before the reresection.
A total of 65 patients who had undergone an unplanned resection of a postoperatively diagnosed soft-tissue sarcoma were treated with RT and/or surgery and retrospectively evaluated for disease progression. Treatment started with RT in 49 cases (75.4%), including 8 cases of no further surgery. A repeat wide resection was performed directly after the initial surgery in 16 patients, followed by RT in 15 of them.
The disease recurred in 7 out of 49 patients (14.3%) who received RT first and in 9 out of 16 (56.25%) who underwent reoperation before RT (P = .001). Disease-free progression was higher in cases of low-grade malignancy (P = .049). A clinical diagnosis of lipoma was associated with a better outcome than a diagnosis of nonlipoma (P = .034). The presence of residual tumor at reoperation did not affect disease control. Patient age, time between symptom onset and diagnosis, hospital level of initial diagnosis (tertiary versus nontertiary), anatomic site, tumor size, and margin status at the initial excisional biopsy were not significantly correlated with the outcome.
Initiating treatment with RT followed by unplanned “oops” resection of soft-tissue sarcoma before the reresection improved disease-free survival as opposed to vice versa.
Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM ...was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC – disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC – disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo – disease progression in 2 patients; Carcinoid – stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET – disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.
Trabectedin is a marine-derived chemotherapy, which has received U.S. Food and Drug Administration approval for use in anthracycline-resistant advanced soft tissue sarcoma (STS), especially ...liposarcoma and leiomyosarcoma (L-sarcomas).
To describe our 10 year real-life experience with trabectedin regarding safety and efficacy in a cohort of 86 patients.
In our study cohort, 46.51% were diagnosed with liposarcoma and 43.02% with leiomyosarcoma. A total of 703 cycles of trabectedin were given, with a median of five cycles per patient (range 1-59). Median overall survival was 13.5 months for the whole cohort, 11 months for liposarcoma patients (range 1-63), and 15 months for leiomyosarcoma patients (range 1-35).
There was no statistically significant difference in progression free survival when stratified according to previous treatment lines given. Trabectedin exhibited a favorable safety profile, with only 22% requiring dose reductions. Grade 3 and higher toxicity was noted in 25% of the patients, mostly due to myelosuppression. There were no treatment-related deaths.
Trabectedin is a safe and effective drug for treating advanced STS. Our results reflect real-life data with patients receiving the drug as a third and even fourth line of treatment, or with a suboptimal performance status, yet achieving impressive clinical benefit rates and survival.
Radiation recall phenomenon (RRP) is an uncommon, late occurring, acute inflammatory skin reaction that emerges in localized areas coincident with previously irradiated radiation therapy (RT) ...treatment fields. RRP has been known to be triggered by a number of chemotherapy agents. To the best of our knowledge, this report is the first description of RRP after administration of the Pfizer-BioNTech vaccine for COVID-19, or any other currently available vaccine against COVID-19. Acute skin reactions were observed in 2 RT patients with differing timelines of RT and vaccinations. In both cases however, the RRP presented within days of the patient receiving the second dose of vaccine. For each RT course, the treatment planning dosimetry of the radiation fields was compared with the area of the observable RRP. RRP developed within the borders of treatment fields where prescription dose constraints were prioritized over skin sparing. Our observation is currently limited to 2 patients. The actual incidence of RRP in conjunction with Pfizer-BioNTech vaccine or any other vaccine against COVID-19 is unknown. For patients with cancer being treated with radiation with significant dose to skin, consideration should be given to the probability of RRP side effects from vaccinations against COVID-19.
Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma. Epidermal growth factor receptor (EGFR) may play a putative role in its pathogenesis, and be targeted for therapeutic ...purposes. The study was aimed at investigating the expression and prognostic influence of EGFR in MPNST. Primary and metastatic MPNSTs were immunostained with antibodies to EGFR. The total EGFR expression (membranous and cytoplasmic) was analyzed by morphometry, grade of positivity and the intensity (score 0–3). An EGFR composite score (range 0–300) was calculated by multiplying the intensity by the grade. A composite score >10 was considered as EGFR overexpression. Score was correlated with clinical behavior. Forty-three percentage of 46 patients with MPNST overexpressed EGFR in the primary tumor, and had a higher prevalence of advanced-stage tumors (≥IIc, 46% vs. 80%,
P
= 0.011). Patients without overexpression had a higher prevalence of tumors with a low mitotic rate (31% vs. 0%,
P
= 0.049). Neurofibromatosis was more prevalent in patients with EGFR overexpression (75% vs. 42%,
P
= 0.007). Five year disease free survival (mean 30.1 vs. 17.4 months,
P
= 0.048), time to progression (mean 9.2 vs. 5.2 months,
P
= 0.005) and 5 year survival (52% vs. 25%,
P
= 0.041, mean 54 vs. 43 months) were significantly higher among patients without overexpression. EGFR appeared to play a role in MPNST progression. EGFR overexpression was correlated with worse prognostic variables and course. Clinical trials of targeting EGFR in MPNST are warranted.
e21097
Background: In recent years, the use of medical cannabis rapidly increased among cancer patients in Israel. Yet, cannabinoid receptors are abundantly expressed on immune cells and modulate ...their activity. It is abundantly being use by metastatic NSCLC patients, shortly following diagnosis and is taken in parallel to first line treatment with ICI. Recent studies suggested that the use of cannabis may reduce the efficacy of ICI. However, these studies were biased by the heterogeneity of patients and the increased use of cannabis specifically in highly symptomatic patients with high disease burden. Methods: We first tested the interaction anti-PD-1 antibody and Δ−9-tetrahydrocannabinol (THC) in a preclinical model consisting of CT26 tumor-bearing mice, and examined the effects on tumor size, T-cell infiltrates, and mice survival. Mice were euthanized when tumor volume reached above 700 mm
3
. Next, we conducted a retrospective study of NSCLC patients, treated at a tertiary center, and included all consecutive patients treated with a single agent pembrolizumab as a first line treatment for advanced disease and evaluated clinical outcome and response to treatment. Results: Studies using the CT26 mice cancer model, indicated a potential beneficial effect for the combination an anti-PD-1 antibody and THC with a median overall survival (OS) of the mice receiving no treatment, THC, anti-PD-1 antibody or their combination being 21 days, 24, 31 days and 54 days, respectively (p < 0.05). Data of 201 NSCLC cancer patients who received first-line single agent pembrolizumab for metastatic disease, 102 (50.7%) patients received cannabis and 99 (49.3%) were cannabis naïve was analyzed. Their median age was 68 for the cannabis treated group and 74 for the cannabis naïve (p = 0.003), 34 (34.3%) in the cannabis treated group and 62 (60.8%) for the cannabis naïve were women (p = 0.002). Similar distribution of histology, smoking status and PDL1 expression was noted between the groups. The efficacy of pembrolizumab, as determined by time to progression (TTP) was similar for cannabis-naïve and cannabis-treated patients (6.1 vs. 4.8 months, respectively, p = 0.386), while OS was higher, though not statistically significant, in the cannabis-naïve group (54 vs. 23.3 months, respectively p = 0.08). Conclusions: Both preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first line monotherapy for advanced NSCLC. The differences in OS can be most likely by attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. While additional validation is required, these data provide somewhat reassuring data regarding the absence of a deleterious effect of cannabis in this clinical setting.
Abstract only
e22530
Background: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracycline (ANT). Cardio-toxicity among patients ...with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutic related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (EF) reduction of > 10%, to a value below 53%. Our objective was to estimate the prevalence of CTRCD among patients with sarcoma, to evaluate echocardiography parameters associated with its development and whether CTRCD is associated with mortality. Methods: Data were collected as part of the International Cardio-Oncology Registry (ICOR), enrolling all patients who were evaluated in the cardio-oncology clinic at our institution. All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. "Preserved EF" group. Results: Among 43 consecutive patients, 6 (14%) developed CTRCD. Elevated left ventricular end systolic diameter (p = 0.007) and a trend of reduced Global Longitudinal Strain (p = 0.092) were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the "Preserved EF" group. In a multivariate analysis, adjusted to age and EF, CTRCD remained a significant predictor for mortality (p = 0.039). Conclusions: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors, and is associated with mortality. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.
The use of medical cannabis has rapidly increased among cancer patients worldwide. Cannabis is often administered concomitantly with cancer medications, including immune checkpoint inhibitors (ICIs). ...As the cannabinoid receptors are abundantly expressed and modulate immune cells, it has been hypothesised that cannabis may attenuate the activity of ICIs. We aimed to assess the effect of cannabis on ICIs' efficiency in patients having non-small cell lung cancer (NSCLC).
The murine model of CT26 tumour-bearing mice treated with an anti-PD-1 antibody and Δ9-tetrahydrocannabinol (THC) was used to evaluate the interaction between THC and ICIs in vivo.
Correlation between use of medical cannabis and clinical outcome was evaluated in a cohort of 201 consecutive metastatic NSCLC patients treated with monotherapy pembrolizumab as a first-line treatment.
Median overall survival (OS) of the mice receiving a control vehicle, THC, anti-PD-1 antibody or their combination was 21, 24, 31 and 54 days, respectively (p < 0.05 for the combination treatment compared to a control vehicle), indicating that THC did not reduce the efficacy of anti-PD-1 therapy.
Of 201 NSCLC patients treated with first-line monotherapy pembrolizumab for metastatic disease, 102 (50.7%) patients received licence for cannabis within the first month of treatment. Cannabis-treated patients were younger compared to the cannabis naïve patients (median age 68 versus 74, p = 0.003), with female predominance (62, 60.8% versus 34, 34.3%, p = 0.002) and with more prevailing brain metastasis (15.7% versus 5%, p = 0.013). Similar distribution of histology, smoking status, ECOG (Eastern Cooperative Oncology Group) and programmed death-ligand 1 expression was noted between the groups. Liver metastases were marginally significant (19.6% versus 10.1%, p = 0.058). The most common indication for cannabis was pain (71%) followed by loss of appetite (34.3%). Time to tumour progression was similar for cannabis-naive and cannabis-treated patients (6.1 versus 5.6 months, respectively, 95% confidence interval, 0.82 to 1.38, p = 0.386), while OS was numerically higher in the cannabis-naive group (54.9 versus 23.6 months) but did not reach statistical significance (95% confidence interval 0.99 to 2.51, p = 0.08). In multivariate analyses, we did not identify cannabis use as an independent predictor factor for mortality.
Preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first-line monotherapy for advanced NSCLC. The differences in OS can most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting.
•Cannabis might alter tumour's microenvironment and, hence, reduce the immune checkpoint inhibitors efficacy.•We investigate this theory in murine models and real-world data.•We found no determinantal effect of this combination in clinic or laboratory.•This conclusion has a great reassuring impact on our patients having non-small cell lung cancer.
Nivolumab is a human IgG4 programmed death (PD)-1 immune checkpoint inhibitor antibody, which is approved in Israel for the treatment of patients with advanced non-small cell lung cancer (NSCLC). It ...is also administered to individuals with disease progression during or after platinum-based chemotherapy, without a need to determine the level of PD-L1 expression in the tumor. The present study aimed to evaluate the survival and efficacy of Nivolumab treatment. A retrospective analysis was performed at a thoracic oncology service in a tertiary referral center (Tel-Aviv Sourasky Medical Center), on patients with NSCLC (squamous and non-squamous). All patients were treated with Nivolumab 3 mg/kg, administered intravenously every 2 weeks as part of a compassionate use program. The survival data was analyzed after 22 months. The overall survival (OS) was 34.9%, while the progression free survival (PFS) was 19.3%. The median PFS from the first dose of Nivolumab to treatment discontinuation was 4 months. A response assessment was performed in the 62 patients who received at least four cycles of Nivolumab, out of the 77 patient cohort. There was a complete response in 1 patient, a partial response in 11 patients, stable disease in 25 patients and progressive disease in 25 patients. The observed response rate of Nivolumab as a service treatment in unselected patients with unknown PD-L1 status NSCLC was 19%. The disease control rate was 60%. In the present study Nivolumab was given to a cohort of patients representing those seen in daily clinical practice, as opposed to a clinical trial setting. Survival and efficacy results strongly support the continued use of Nivolumab as a treatment for NSCLC.
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