A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.

AROME-ESO Oncology Consensus Conference: access to cancer care innovations in countries with limited resources. Association of Radiotherapy and Oncology of the Mediterranean Area (AROME-Paris) and European School of Oncology (ESO - Milan).

PURPOSE: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference. METHODS: Cancer prevention and treatment strategies were discussed according to existing international guidelines. The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/middle-income Mediterranean countries. The results from the votes of 65 oncology experts, coming from 16 countries and 33 institutions have been analysed and access priorities classified accordingly. RESULTS: Ninety six percent of the proposed general recommendations concerning national health care strategies, oncology education, and treatment organization were considered to be high priorities. Regarding access to systemic treatments, 41% of the drugs without validated predictive markers and 53% of those with validated predictive markers were considered to be 1st level priority. Only 4 biological tests were considered to be 1st level priority to access to innovation. CONCLUSIONS: AROME-ESO consensus offers to cancer specialists from developing countries a basis for discussion with health authorities and payers on the prioritization of access to innovations in cancer care.

Outcome and Predictive Factors in Uterine Carcinosarcoma Using Postoperative Radiotherapy: A Rare Cancer Network Study.

Uterine carcinosarcomas (UCS) are rare tumors. Consensus regarding therapeutic management in non-metastatic disease is lacking. This study reports on outcome and predictive factors when using postoperative radiotherapy. We analyzed a retrospective analysis in 124 women treated between 1987-2007 in the framework of the Rare-Cancer-Network. Median follow-up was 27 months. Postoperative pelvic EBRT was administered in 105 women (85%) and 92 patients (74%) received exclusive or additional vaginal brachytherapy. Five-year overall survival (OS), disease-free survival (DFS), cancer specific survival (CSS) and locoregional control (LRC) were 51.6% (95% CI 35-73%), 53.7% (39-71%), 58.6% (38-74%) and 48% (38-67%). Multivariate analysis showed that external beam radiation therapy (EBRT) >50Gy was an independent prognostic factor for better OS (P=0.03), CSS (P=0.02) and LRC (P=0.01). Relative risks (RR) for better OS (P=0.02), DFS (P=0.04) and LRC (P=0.01) were significantly associated with younger age (≤60 years). Higher brachytherapy (BT)-dose (>9Gy) improved DFS (P=0.04) and LRC (P=0.008). We concluded that UCS has high systemic failure rate. Local relapse was reduced by a relative risk factor of over three in all stages of diseases when using higher doses for EBRT and brachytherapy. Postoperative RT was most effective in UCS stage I/II-diseases.

Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.

BACKGROUND: The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS: We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS: Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS: In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).

Primary systemic therapy and whole breast irradiation for locally advanced breast cancer: a systematic review.

The current management of locally advanced breast cancer (LABC) is based on tri-modality treatment including chemotherapy, radiotherapy and surgery. The concept of preoperative concurrent or sequential chemoradiation for LABC was initially reported more than a decade ago; however this concept did not gain popularity because of the low benefit/risk ratio and the lack of strong data supporting the concept. The purpose of the current systematic review was to explore the published data about preoperative chemoradiation (sequential and/or concurrent) using whole breast irradiation in terms of toxicity and outcome.

Tolerance of the vaginal vault to high-dose rate brachytherapy and concomitant chemo-pelvic irradiation: Long-term perspective.

AIM/BACKGROUND: We sought to determine the tolerance level and complication rates of the vaginal vault to combined high-dose-rate intra-cavitary brachytherapy with concomitant chemo-radiotherapy. PATIENTS AND METHODS: A retrospective review of medical records of all the patients who received definitive chemo-radiotherapy for cervical cancer between 1998 and 2002 was undertaken. The records were reviewed for doses and for radiation-associated early and late sequelae of the vagina, rectum and bladder. Cumulative biological effective dose was calculated for two reference vaginal surface points. RESULTS: Fifty patients were included. Average age at diagnosis was 54 years. Median follow-up was 59 months. There were no recorded instances of acute grade IV toxicity. Maximal high-dose-rate vaginal surface dose (upper central point) was 103 Gy, and maximal brachytherapy lateral surface dose was 70 Gy. Maximal cumulative biological effective dose for the lateral surface reference point was 465.5 Gy3, and the maximal cumulative biological effective dose for the superior reference point was 878.6 Gy3. There were no cases of vaginal necrosis or fistulas, and no cases of grade IV late vaginal, rectal or bladder toxicity. No correlation was found between the maximal vaginal surface dose and vaginal, rectal or bladder toxicity. CONCLUSIONS: The maximal surface HDR brachytherapy dose of 103 Gy and the maximal cBED of 878.6 Gy3 were not associated with fistula or necrosis or other grade 3-4 vaginal complications. Concomitant chemo-radiotherapy, including pelvic radiotherapy and high-dose-rate intracavitary brachytherapy, is relatively safe for cervical cancer patients.

Magnetic resonance-guided focused ultrasound for patients with painful bone metastases: phase III trial results.

BACKGROUND: Pain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue ablation for palliation of pain due to bone metastases. METHODS: Patients with painful bone metastases were randomly assigned 3:1 to receive MRgFUS sonication or placebo. The primary endpoint was improvement in self-reported pain score without increase of pain medication 3 months after treatment and was analyzed by Fisher's exact test. Components of the response composite, Numerical Rating Scale for pain (NRS) and morphine equivalent daily dose intake, were analyzed by t test and Wilcoxon rank-sum test, respectively. Brief Pain Inventory (BPI-QoL), a measure of functional interference of pain on quality of life, was compared between MRgFUS and placebo by t test. Statistical tests were two-sided. RESULTS: One hundred forty-seven subjects were enrolled, with 112 and 35 randomly assigned to MRgFUS and placebo treatments, respectively. Response rate for the primary endpoint was 64.3% in the MRgFUS arm and 20.0% in the placebo arm (P < .001). MRgFUS was also superior to placebo at 3 months on the secondary endpoints assessing worst score NRS (P < .001) and the BPI-QoL (P < .001). The most common treatment-related adverse event (AE) was sonication pain, which occurred in 32.1% of MRgFUS patients. Two patients had pathological fractures, one patient had third-degree skin burn, and one patient suffered from neuropathy. Overall 60.3% of all AEs resolved on the treatment day. CONCLUSIONS: This multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.

Toxicity of induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil for advanced head and neck cancer.

BACKGROUND: The role of induction chemotherapy in advanced squamous cell carcinoma of the head and neck (SCCHN) is under constant debate. Surgery, radiotherapy, chemotherapy, and targeted therapies are part of the treatment strategy in these patients, but their sequence remains to be defined. OBJECTIVES: To evaluate the feasibility of induction chemotherapy with docetaxel-cisplatin-5-flurouracil (TPF) followed by external beam radiotherapy (EBRT) with concomitant chemotherapy or cetuximab (ERT) in the treatment of patients with advanced SCCHN. METHODS: We reviewed the data of all patients with advanced SCCHN, stage III and IV, treated in 2007-2010. Tolerability was assessed and scored according to the proportion of patients completing the planned study protocol. Toxicity was scored using the U.S. National Cancer Institute Common Toxicity Criteria (version 4) for classification of adverse events. RESULTS: The study included 53 patients. TPF was initiated at a reduced dose in 13 patients (25%). Twenty-two patients (41.5%) received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) and 42 (77%) completed treatment according to schedule. During the induction phase one patient (2%) died and 24 (45%) had one or more grade 3-4 complications. The number of patients who developed neutropenia was lower in the group that received primary GCSF prophylaxis. Secondary dose reductions were required in 21% of the patients. CONCLUSIONS: Induction TPF was associated with grade 3-4 toxicity. Prophylaxis with GCSF should be part of the treatment regimen.

Hippocampal-sparing whole-brain radiotherapy using Elekta equipment.

The purpose of this study was to evaluate the feasibility of hippocampal-sparing whole-brain radiotherapy (HS WBRT) using the Elekta Infinity linear accelerator and Monaco treatment planning system (TPS). Ten treatment plans were created for HS-WBRT to a dose of 30 Gy (10 fractions). RTOG 0933 recommendations were applied for treatment planning. Intensity-modulated radiotherapy (IMRT) plans for the Elekta Infinity linear accelerator were created using Monaco 3.1 TPS-based on a nine-field arrangement and step-and-shoot delivery method. Plan evaluation was performed using D2% and D98% for the whole-brain PTV (defined as whole brain excluding hippocampus avoidance region), D100% and maximum dose to the hippocampus, and maximum dose to optic nerves and chiasm. Homogeneity index (HI) defined as (D2%-D98%)/Dmedian was used to quantify dose homogeneity in the PTV. The whole-brain PTV D2% mean value was 37.28 Gy (range 36.95-37.49Gy), and D98% mean value was 25.37 Gy (range 25.40-25.89 Gy). The hippocampus D100% mean value was 8.37 Gy (range 7.48-8.97 Gy) and the hippocampus maximum dose mean value was 14.35 Gy (range 13.48-15.40 Gy). The maximum dose to optic nerves and optic chiasm for all patients did not exceed 37.50 Gy. HI mean value was 0.36 (range 0.34-0.37). Mean number of segments was 105 (range 88-122) and mean number of monitor units was 1724 (range 1622-1914). Gamma evaluation showed that all plans passed 3%, 3 mm criteria with more than 99% of the measured points. These results indicate that Elekta equipment (Elekta Infinity linac and Monaco TPS) can be used for HS WBRT planning according to compliance criteria defined by the RTOG 0933 protocol.

"The Infinite Maze" of breast cancer, signaling pathways and radioresistance.

The parallel growth in our understanding of tumor biology and genetics might be the key to understanding local recurrence after optimal treatment is applied. Data suggest that genetic alterations and breast cancer molecular subtypes have an effect on radiotherapy efficacy and that the HER2, EGFR/PI3K/Akt signaling pathways play a pivotal role in modulation of post-irradiation survival. These pathways have been found to be involved in radiosensitivity and/or radioresistance, tumor cell proliferation, and hypoxia. Therefore, affecting the functional activity of key players combined with radiotherapy might be the future of breast irradiation.

Targeted therapy with low doses of 131I-MIBG is effective for disease palliation in highly refractory neuroblastoma.

BACKGROUND: Palliative treatment ore remains a significant clinical problem. OBJECTIVES: To retrospectively determine the clinical response to 131I-MIBG therapy at low doses in patients with refractory neuroblastoma. METHODS: We performed a retrospective chart review of 10 patients with neuroblastoma treated with 1311-MIBG at Rambam Health Care Campus from 1994 to 2012. Clinical data, number of 131I-MIBG courses delivered, toxicities, and clinical responses were reviewed. MIBG scan was performed after each course. RESULTS: Twenty-one courses of 131I-MIBG were delivered to 10 patients (3 girls, 7 boys). Their mean age was 3.8 years (range 1.5-6 years). All patients received several protocols of chemotherapy including the high dose form. Three patients received three courses of 131I-MIBG with a minimum of 6 weeks between each course, five patients received two courses, and two patients received only one course. An objective response to the first course was obtained in nine patients and to the second course in six of eight, and in three children who underwent the third course the pain decreased. One patient has no evidence of disease, four are alive with disease, and five died of the disease. No unanticipated toxicities were observed. CONCLUSIONS: Low dose 131I-MIBG is an effective and relatively non-toxic treatment in neuroblastoma disease palliation. Rapid and reproducible pain relief with 131I-MIBG was obtained in most of the children. Treatment with systemic radiotherapy in the form of low dose 131I-MIBG was easy to perform and effective in cases of disseminated neuroblastoma, demonstrating that this primary therapy can be used for palliative purposes.

Breast-conserving surgery and intraoperative electron radiotherapy in early breast cancer: experience at the Rambam Health Care Campus.

BACKGROUND: Local recurrences after breast-conserving surgery occur mostly at the site of the primary carcinoma. The main objective of postoperative radiotherapy is sterilization of residual cancer cells. Whole-breast radiotherapy is the standard of care, but its utility has recently been challenged in favor of radiotherapy limited to the area at highest risk of recurrence. Intraoperative electron radiotherapy (IOeRT) is an innovative technique for accelerated partial breast irradiation (APBI) that is applied to selected patients affected by early breast cancer. OBJECTIVES: To describe our experience with IOeRT at the Rambam Health Care Campus in Haifa since we began utilizing this modality in 2006. METHODS: From April 2006 to September 2010, 31 patients affected by unifocal invasive duct breast carcinoma < or = 2 cm diameter received wide local resection followed by intraoperative radiotherapy with electrons. Patients were evaluated for early and late complications, and other events, 1 month after surgery and every 3 months thereafter for the duration of the first 2 years. RESULTS: After a mean follow-up of 36 months, seven patients developed mild breast fibrosis and three suffered from mild postoperative infection. Rib fractures were observed in four patients before routine lead shielding was initiated. Additional whole-breast irradiation was given to four patients. None of the patients developed local recurrences or other ipsilateral cancers. Similarly, no contralateral cancers or distant metastases were observed. CONCLUSIONS: Intraoperative electron radiotherapy may be an alternative to external beam radiation therapy in an appropriate selected group of early-stage breast cancer patients. However, long-term results of clinical trials are required to better evaluate the indications and utility of this technique in the management of breast cancer.

The role of imaging in the management of non-metastatic cervical cancer.

The role of the physician is to choose the best treatment in terms of survival benefits with the lowest toxicity. Surgery is indicated for early disease, but insufficient pretreatment evaluation may result in an unnecessary procedure or the need for adjuvant therapy. Appropriate imaging may aid in these decisions. Involvement of imaging in radiotherapy allows more accurate and localized irradiation. Confirmation of correct patient positioning is an integral part of radiotherapy, and in the era of modern imaging, newer image-guided techniques are used to ensure adequate positioning of the target. It seems that the evolution of radiotherapy in the era of advanced imaging and the field of adaptive radiotherapy in uterine cervical cancer is a result of the availability of these novel modalities. This review discusses the role of imaging in the treatment planning of cervical cancer.

Brain metastasis of nasopharyngeal carcinoma: a case report and literature review.

Central nervous system metastases from nasopharyngeal carcinoma (NPC) are uncommon. The patient presented was diagnosed with aggressive advanced NPC resistant to treatment and complicated by a solitary brain metastasis. A PubMed database search was conducted to review the existing literature regarding brain metastases of NPC, using the search terms "nasopharyngeal neoplasia," "nasopharyngeal carcinoma," "nasopharynx," "radiotherapy," "central nervous system," and "brain" in section of "Title/Abstract." The articles were first evaluated by title and then by abstract, and thereafter appropriate manuscripts were evaluated by full text. References of the published papers were also reviewed.

Current principles for radiotherapy in cervical cancer.

Cancer of the uterine cervix is most common in countries that do not have access to cervical cancer screening and prevention programs. Treatment of cervical cancer varies significantly between countries (adjusted to stage) and is dependent on medical resources. Radiotherapy for the treatment of gynecological malignancy has been used with different techniques for treating the local tumor and regional lymph nodes. This review discusses recommendations of radiotherapy for cervical cancer according to stage.