Weekly Carboplatin and Paclitaxel: A Retrospective Comparison with the Three-Weekly Schedule in First-Line Treatment of Ovarian Cancer.

BACKGROUND: Conventional first-line combination therapy for ovarian cancer comprises 6 cycles of adjuvant or neoadjuvant carboplatin (AUC5-6) with paclitaxel (175 mg/m2 ) every 3 weeks (PC-3W). Weekly scheduling of paclitaxel may maximize its antiangiogenic effect and reduce adverse effects. We compared the efficacy and safety of PC-3W with a modified protocol of weekly paclitaxel 80 mg/m2 and weekly carboplatin AUC2 administered on days 1, 8, and 15 in a 28-day cycle (i.e., with 1 week off-treatment [PC-W]). MATERIALS AND METHODS: Medical records of consecutive patients treated between 2000 and 2018 were reviewed; 707 patients were analyzed for demographic and clinical characteristics, effectiveness and toxicity. RESULTS: PC-3W was administered to 402 patients (median age, 60.5 years) and PC-W to 305 patients (median age, 62.5 years). Most patients (91.4%) were diagnosed at stage III-IV. Notwithstanding a higher proportion of residual disease and older patients in the PC-W group, median progression-free survival was 21.4 months and 13.2 months for PC-W and PC-3W, respectively; median overall survival was 75.2 and 54.0 months for PC-W and PC-3W, respectively. Cox proportional hazards model indicated improved survival for patients treated with PC-W (hazard ratio, 0.54). Similar results were observed for older patients diagnosed at ≥75 years. PC-W demonstrated a better safety profile, with lower incidence of neuropathy, neutropenia, and alopecia. CONCLUSION: PC-W is as active and better tolerated than the standard PC-3W regimen. PC-W may serve as an alternative option for elderly or frail patients. IMPLICATIONS FOR PRACTICE: Weekly scheduling of paclitaxel 80 mg/m2 and carboplatin AUC2, administered on days 1, 8, and 15 in a 28-day cycle (PC-W) for first-line therapy for advanced ovarian cancer, is as active and better tolerated than the standard regimen of carboplatin and paclitaxel (175 mg/m2 ) every 3 weeks (PC-3W). It is possible that the weekly holiday on day 21 in the PC-W regimen may ensure better completion rates (which may result in treatment delays for toxicity in PC-3W). The results of this retrospective analysis highlight the weekly regimen as a valid treatment option, especially for elderly patients and those with significant comorbidities.

Volumetric Modulated Arc Therapy as an Example of the Advanced Capability of Modern Radiotherapy.

BACKGROUND: Family physicians and internal medicine specialists play an essential role in treating cancer patients. Modern technological advances in radiotherapy are not widely appreciated by primary care physicians. Bone metastases are a frequent complication of cancer. Palliative radiation therapy, as a component of modern advances in radiation treatments, should not subject normal bodily structures to excessive doses of irradiation. The sacrum is a common destination site for bone metastases, yet its concave shape along with its proximity to the rectum, intestines, and femoral heads creates treatment-planning challenges. OBJECTIVES: To investigated whether the volumetric modulated arc therapy (VMAT) technique is preferable to more conventional radiation strategies. METHODS: The study comprised 22 patients with sacral metastases who were consecutively treated between 2013 and 2014. Two plans were generated for the comparison: three-dimensional (3D) and VMAT. RESULTS: The planning target volume (PTV) coverage of the sacrum was identical in VMAT and 3D planning. The median values for the rectal dose for 3D and VMAT were 11.34 ± 5.14 Gy and 7.7 ± 2.76 Gy, respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22 cases, while the upper pole of the rectum ended at the level above S3 in just 3 cases. CONCLUSIONS: Radiation therapy continues to be an integral component of the palliative armamentarium against painful metastases. Radiation oncologist, in conjunction with referral physicians, can tailor treatment plans to reflect the needs of a given patient.

Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience.

BACKGROUND: Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care. OBJECTIVE: To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel. PATIENTS AND METHODS: This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. RESULTS: The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1-4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12-1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected. CONCLUSIONS: Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

Stereotactic radiosurgery (SRS) in high-grade glioma: judicious selection of small target volumes improves results.

We present a retrospective review of 55 Stereotactic Radiosurgery (SRS) procedures performed in 47 consecutive patients with high-grade glioma (HGG). Thirty-three (70.2%) patients were diagnosed with glioblastoma and 14 (29.8%) with grade III glioma. The indications for SRS were small (up to 30 mm in diameter) locally progressing lesions in 32/47 (68%) or new distant lesions in 15/47 (32%) patients. The median target volume was 2.2 cc (0.2-9.5 cc) and the median prescription dose was 18 Gy (14-24 Gy). Three patients (5.5% incidence in 55 treatments) developed radiation necrosis. In eight cases (17%) patients received a second salvage SRS treatment to nine new lesions detected during follow-up. In 22/55 SRS treatments (40.0%) patients received concurrent chemo- or biological therapy, including temozolamide (TMZ) (15 patients), bevacizumab (BVZ) (6 patients) and carboplatin in one patient. Median time to progression after SRS was 5.0 months (1.0-96.4). Median survival time after SRS was 15.9 months (2.3-109.3) overall median survival (since diagnosis) was 37.4 months (9.6-193.6 months). Long-lasting responses (>12 months) after SRS were observed in 25/46 (54.3%) patients. We compared a matched (histology, age, KPS) cohort of patients with recurrent HGG treated with BVZ alone with the current study group. Median survival was significantly longer for SRS treated patients compared to the BVZ only cohort (12.6 vs. 7.3 months, p = 0.0102). SRS may be considered an effective salvage procedure for selected patients with small volume, recurrent high-grade gliomas. Long-term radiological control was observed in more than 50% of the patients.

Patterns of Failure after Stereotactic Radiosurgery of the Resection Cavity Following Surgical Removal of Brain Metastases.

BACKGROUND: Whole brain radiation treatment (WBRT) is considered standard treatment for BM. However, exposing large volumes of normal brain tissue to irradiation can cause neurotoxicity. This study describes our experience with 100 consecutive patients with brain metastases who were managed with surgical extirpation followed by stereotactic radiosurgery (SRS) to the resection cavity. METHODS: Patients with 1-3 brain metastases (BM), who underwent resection of 1-2 BM between June 2005 and December 2013, were treated with SRS directed to the tumor cavity and for any synchronous BM. Local and distant treatment failures were determined based on neuroimaging. Kaplan-Meier curves were generated for local and distant failure rates and overall survival. RESULTS: One hundred and two resection cavities were treated with SRS in 100 consecutive patients. Thirty-two additional synchronous metastases were treated in 27 patients during the same session. The median overall survival was 18.9 months. Local control rate at 1 year was 84%. Longer delays between surgery and SRS were associated with increased risk of local failure (hazard ratio, -1.46; P = 0.02). Distant progression occurred in 44% of the patients at a mean of 8.8 ± 6.6 months after SRS treatment. Ten cases of leptomeningeal spread occurred around the resection cavities (9.8%). Central nervous system failure was not significantly associated with survival. Multivariate Cox regression analysis showed that recursive partitioning analysis and active systemic disease were significantly associated with survival. CONCLUSION: The strategy described provides acceptable local disease control when compared with WBRT following surgery. This approach can delay and even annul WBRT in the majority of selected BM patients, especially recursive partitioning analysis class I patients. SRS should be scheduled as soon as possible after surgery.

Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study.

BACKGROUND: Approximately 70% of women diagnosed with advanced-stage ovarian cancer experience disease recurrence. Survival data were compared between a group of recurrent epithelial ovarian cancer (rEOC) patients treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) and a matched group of rEOC patients treated by systemic chemotherapy only (without surgery). Treatment outcome in relation to the patients' BRCA status was compared. METHODS: Twenty-seven rEOC patients treated by cytoreduction and HIPEC were selected from our database and matched (1:3) with 84 rEOC patients treated with chemotherapy only. Progression-free survival (PFS) and overall survival (OS) in the two groups were analyzed and compared. RESULTS: The estimated median PFS was 15 months in the HIPEC group and 6 months in the systemic chemotherapy group (P = 0.001). The median OS following HIPEC treatment has not been reached, since more than 70% of the women were alive at the time of analysis. The 5-year survival rate was significantly higher in the HIPEC treated patients compared to that of the controls (79% vs. 45%, P = 0.016). BRCA status did not affect PFS. CONCLUSIONS: HIPEC after surgical cytoreduction in patients with rEOC appears beneficial compared to systemic chemotherapy treatment alone. The benefit is even greater in BRCA mutation carriers.

Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line?

Glioblastoma is a malignant tumor characterized by a rapid proliferation rate. Contemporary multi-modality treatment consists of maximal surgical resection followed by radiation therapy (RT) combined with cytotoxic chemotherapy. The optimal timing of these different steps is not known. Four studies from the pre-temozolomide era, encompassing a total of 4,584 subjects, have examined the consequences of a delay between resection and starting RT. Whereas the two small single-institution studies found this delay to be detrimental, two large multi-institutional studies found delay to be either slightly beneficial or at least not harmful. Here, we critically compare the methodologies and results presented in these studies, and include a novel analysis of the combined datasets. We conclude that moderate wait periods (up to 4-6 weeks post-operatively) are safe and may be modestly beneficial. Conversely, there is no evidence to justify waiting longer than 6 weeks. Underlying radiobiological principles are discussed.

Improved treatment of the breast and supraclavicular fossa based on a simple geometrical principle.

In breast cancer, nodal irradiation has become routine, but adds time and creates concerns for field overlap if the "match" is not accurate. We developed a technique to address these issues by using only one isocenter for both areas. Tangents are designed at simulation. The isocenter is then shifted to the upper border of the breast using a straightforward geometrical calculation. After determining the new isocenter, fields are recreated wherein the tangents are treated with a quarter beam and the supraclavicular field fashioned with a half-beam block. The gantry, collimator, and couch angles of the supraclavicular field are adjusted to achieve an accurate match. Ten patients were evaluated. Doses to the spinal cord and brachial plexus were lowered relative to conventional techniques. The hot spots were not augmented. In comparison with standard arrangements, setup time decreased. Accurate matching was consistently achieved and verified by portal imaging. A new approach for treating the supraclavicular fossa is easily executed. Advantages include negligible doses to the critical neural structures (i.e., spinal cord and brachial plexus), optimized matchline, and reduced setup time.

Radiosurgical treatment planning of AVM following embolization with Onyx: possible dosage error in treatment planning can be averted.

Treatment of arteriovenous malformations (AVM) of the brain is challenging due to the size and location of the nidus-proper and its proximity to the cerebrovascular circulation. Recent advances in catheter techniques and new embolization materials such as Onyx (a liquid agent that is less adhesive and slowly polymerizing) have increased the probability of achieving obliteration. When planning radiosurgical cases following such embolization, however, one must be cognizant of the distortions introduced by this novel substance on imaging studies. A sample of Onyx was irradiated to define the attenuation per mm thickness. The difference in attenuation compared to water was determined. Dose calculations were performed using 3 methods of inhomogeneity corrections. Homogeneous calculations were compared to "standard" heterogeneity corrections and to "modified" heterogeneity corrections by assigning individual electron densities to the normal brain and the Onyx. The difference between the attenuation of water in comparison to the Onyx was approximately 3% for beam energy of 6 MV. Best calculation results were achieved when using the modified inhomogeneity corrections which were based on the actual attenuation of the Onyx. The use of Onyx caused significant image artifact on MR and especially CT. As such, a correction must be manually introduced into the planning system to account for this potential error. Otherwise, dose calculation may be unreliable and could have dire consequences for patients receiving high doses of radiotherapy.

Assessing the effectiveness of Dead Sea products as prophylactic agents for acute radiochemotherapy-induced skin and mucosal toxicity in patients with head and neck cancers: a phase 2 study.

BACKGROUND: Mucositis and dermatitis are frequently encountered in patients treated with radiochemotherapy. Dead Sea products that contain minerals and other properties have proven effective in treating various skin diseases. OBJECTIVES: To evaluate the effectiveness of Dead Sea products in reducing acute radiochemotherapy-induced side effects in patients with head and neck cancer. METHODS: In this phase 2 study we compared the outcomes in 24 treated patients and 30 conventionally treated patients matched for age, tumor site, and type of treatment. The Dead Sea products comprised a mouthwash solution (Lenom) and a skin cream (Solaris) used three times daily for 1 week before, during, and up to 2 weeks after completion of radiotherapy. Mucositis and dermatitis were evaluated using common toxicity criteria. RESULTS: Thirteen treated patients (54%) had grade 1-2 and none had 3-4 mucositis, while 17 controls (57%) had grade 1-2 and 4 (13%) had grade 3-4 mucositis. Thirteen treated patients (54%) had grade 1-2 dermatitis; there was no instance of grade 3-4 dermatitis, while 11 patients in the control group (37%) had grade 1-2 and 5 (17%) had grade 3-4 dermatitis. More patients in the control arm needed a break than did patients in the treatment the control arm needed a break than did patients in the treatment arm (P = 0.034). CONCLUSIONS: The two Dead Sea products tested decreased skin and mucosal toxicity in head and neck cancer patients receiving radiochemotherapy.