A phantom study investigating effective strategies for reducing fetal dose in pregnant patients with head and neck cancer.

PURPOSE: To measure the out-of-field doses for various treatment planning techniques and assess the impact on fetal dose with and without the use of custom shielding. MATERIALS AND METHODS: A total of six treatment plans were generated with different treatment techniques such as 3-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT), utilizing both 6 MV flattened beams and flattening filter-free (FFF) beams. The measurements were carried out both out-of-field at the surface and at depth to assess the dose reduction achieved by removing the flattening filter and incorporating shielding. RESULTS: The custom-made frame shielding can effectively reduce the surface dose with a maximum reduction of 15.2% observed in VMAT plans and achieve a maximum reduction of 100% for cone beam computed tomography (CBCT) imaging. Out-of-field dose measurements conducted at depth, positioned 58 cm inferior to the target isocenter, reveal that the shielding effectiveness consistently remains the greatest for 3DCRT technique. A maximum reduction of 21% is observed when utilizing a flattening filter-free beam. CONCLUSION: The results of this study indicate that the 3DCRT technique exhibits the least amount of scatter radiation both near and far from the treatment isocenter, which is the most suitable approach for radiation therapy of pregnant patients. In cases where meeting dose constraints for critical organs becomes challenging, VMAT technique emerges as the most suitable treatment technique for reducing out-of-field doses. Additionally, a flattening filter-free beam significantly reduces out-of-field doses due to lower contributions from head scatter.

A review on fetal dose in Radiotherapy: A historical to contemporary perspective.

This paper aims to review on fetal dose in radiotherapy and extends and updates on a previous work1 to include proton therapy. Out-of-field doses, which are the doses received by regions outside of the treatment field, are unavoidable regardless of the treatment modalities used during radiotherapy. In the case of pregnant patients, fetal dose is a major concern as it has long been recognized that fetuses exposed to radiation have a higher probability of suffering from adverse effects such as anatomical malformations and even fetal death, especially when the 0.1Gy threshold is exceeded. In spite of the low occurrence of cancer during pregnancy, the radiotherapy team should be equipped with the necessary knowledge to deal with fetal dose. This is crucial so as to ensure that the fetus is adequately protected while not compromising the patient treatment outcomes. In this review paper, various aspects of fetal dose will be discussed ranging from biological, clinical to the physics aspects. Other than fetal dose resulting from conventional photon therapy, this paper will also extend the discussion to modern treatment modalities and techniques, namely proton therapy and image-guided radiotherapy, all of which have seen a significant increase in use in current radiotherapy. This review is expected to provide readers with a comprehensive understanding of fetal dose in radiotherapy, and to be fully aware of the steps to be taken in providing radiotherapy for pregnant patients.

Radiotherapy and pregnancy.

We present the updated recommendations of the French society for radiation oncology on radiotherapy and pregnancy. The occurrence of cancer during pregnancy is a rare event (approximately 1 in 1000 pregnancies). The risks for the embryo or the foetus depend on the gestational age at the time of irradiation. The main risks are malformations with microcephaly and mental retardation. There is also a risk of radiation-induced cancer in the unborn child. In the case of only supradiaphragmatic irradiation, radiotherapy can be performed most often in pregnant women without risk to the foetus. On the other hand, in the case of an indication for subdiaphragmatic irradiation, therapeutic termination of the pregnancy should be proposed. In all cases, when radiotherapy is chosen, a phantom estimation of the dose delivered to the foetus, confirmed by in vivo measurement, is recommended. Conformational radiotherapy is the preferred technique because of the lower dose delivered to the foetus (except in tumour locations where other techniques such as IMRT are recommended).

Pregnancy Does not Affect the Prognoses of Differentiated Thyroid Cancer Patients With Lung Metastases.

CONTEXT: Pregnancy-related hormones may stimulate thyroid cancer growth, but whether pregnancy affects the prognoses of patients with lung metastases from differentiated thyroid cancer (DTC-LM) after surgery and radioiodine therapy is unclear. OBJECTIVE: To assess the impact of pregnancy on DTC-LM through the comparison of prognoses between female patients with DTC-LM who did and did not become pregnant after surgery and radioiodine therapy. METHODS: We retrospectively analyzed the records of 124 female patients aged 16 to 35 years who underwent surgery and radioiodine therapy for DTC-LM. These patients were divided into pregnancy group (n = 37) and nonpregnancy group (n = 87) according to whether they became pregnant after surgery and radioiodine therapy, regardless of whether they had a pregnant history before treatment. RESULTS: The 5- and 10-year progression-free survival rates were 94.52% and 63.22% in pregnancy group versus 89.82% and 58.13% in nonpregnancy group. The 5- and 10-year cumulative overall survival rates of pregnancy group were 97.30% and 85.77% versus 93.50% and 81.95% in nonpregnancy group (all P > 0.05). The median time of follow-up in the pregnancy and nonpregnancy groups was 82 months (25-136 months) and 68 months (13-133 months), respectively. Non-radioiodine-avid LM and primary tumors needing repeated resection were independent predictors of poor progression-free survival for patients in pregnancy group. CONCLUSION: Pregnancy does not affect the prognoses of patients with DTC-LM after surgery and radioiodine therapy. Non-radioiodine-avid LM and repeated primary tumor surgeries are independent risk factors for poor prognoses of pregnant patients.

Surgery for Pregnancy-Associated Breast Cancer.

Surgery in the form of both mastectomy and breast conservation is the main step in the treatment of breast cancer. Numerous studies have shown an equivalent long-term survival for breast conserving surgery (BCS) and mastectomy . Patients desire and tumor characteristics, especially size and multicentricity, are the key factors that affect the decision between these two types of surgery . Patients with any contraindication for radiotherapy or previous history of radiation to the breast field are not suitable for BCS . There are few absolute contraindications for BCS , and early pregnancy is listed among them; mastectomy is preferred in the first trimester of pregnancy to avoid the impact of delaying radiation therapy on outcome of the cancer.

Radiotherapy in Pregnancy-Associated Breast Cancer.

Breast radiotherapy during pregnancy is a matter of debate as both the efficacy of treatment and the safety of the developing fetus should be considered. Currently there is not enough data to support the safety of in-utero exposure to radiation even with modern radiotherapy techniques. So it is highly recommended that breast radiotherapy is postponed to after delivery, though it might be considered in very selected patients according to risk-benefit assessment.

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy.

BACKGROUND: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. METHODS: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. RESULTS: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5-101.8, versus 104.4, 95% CI: 100.4-108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6-4.3, versus 4.5, 95% CI: 4.1-4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). CONCLUSIONS: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, NCT00330447.

[Measurement of out-of-field dose to the uterus during proton therapy of the head and neck]. / Mesure de la dose délivrée hors champ à l'utérus lors d'un traitement ORL par protons.

The decision to irradiate during pregnancy is based on a risk benefit compromise of two kinds: maternal risk and fetal risk. The aim of this work is to determine the foetal risk, and uterine dose measurement in proton therapy. Foetal exposure during treatment is linked to two sources: the treatment phase, and the repositioning phase. An Alderson-Rando anthropomorphic ghost (170cm, 74kg) was positioned on the table in the treatment position. A tissue-equivalent proportional counter (TEPC), adapted to the analysis of complex radiation fields (neutron and photonics), was used to determine the irradiation related to the treatment phase. An AT1123 radiation survey meter was used to measure photons generated by X-ray radiation. I dosimetry was proposed using radio-photoluminescent dosimeters, allowing for a daily check of the dose received in the uterus. The treatment phase produces higher uterine doses than the positioning phase, but these remain very low. The equivalent dose received in the uterus for the entire treatment is estimated at 840 µSv. Using a methodology for measuring the out-of-field dose with pencil beam scanning proton therapy, the foetal dose in the first trimester was well below the acceptance dose of 100 mGy determined by the International Commission on Radiological Protection.

A Case Report of Adult Pineoblastoma Occurring in a Pregnant Woman.

BACKGROUND/AIM: Pineoblastoma of the adult age is an uncommon tumor with only 200 cases reported. A standardized approach for an optimal adjuvant strategy is currently lacking. The case presented herein also deals with the issue of central nervous system tumors in pregnancy. CASE REPORT: A 21-year-old pregnant woman presented with massive hydrocephalus due to a mass in the pineal region detected with MRI. After positioning an urgent ventricular derivation, a cesarean section was performed. During a third ventriculocisternostomy, a biopsy revealed a pineoblastoma. After a maximal safe resection, postoperative craniospinal irradiation for a total dose of 36 Gy plus a sequential boost to the tumor bed to 54 Gy, and adjuvant chemotherapy with CDDP plus CCNU plus vincristine were performed. After one year, the patient is alive with no evidence of disease. CONCLUSION: The use of adjuvant radio-chemotherapy provided excellent outcomes in our case. The advanced gestational age facilitated the choice of the therapeutic strategy.

Modern radiotherapy in cancer treatment during pregnancy.

Breast cancer, gynecological malignancies and lymphomas are the most frequently diagnosed tumors in pregnant women. The feasibility of radiotherapy during pregnancy remains a subject of debate and clinicians continue to hesitate on this approach, trying to avoid radiotherapy in most cases. Since the 1990s, several technological advances, including intensity modulated and image guided radiation delivery, have been implemented in radiation oncology to improve the radiation treatment in terms of effectiveness and tolerability. It remains uncertain which short- and long-term health effects the radiation exposure of the fetus may have through advanced radiotherapy techniques. The present systematic literature review aims to summarize the limited current evidences of the feasibility and clinical results of "modern" radiotherapy procedures for the treatment of the most frequently diagnosed tumors in pregnant women.

[Diagnostics, treatment and prognosis in breast cancer during pregnancy].

Breast cancer is the second most common form of cancer diagnosed during pregnancy. The diagnosis and treatment of breast cancer during pregnancy requires multidisciplinary efforts to treat the cancer while protecting the foetus. Pregnancy-related changes in the breast make the diagnosis particularly challenging. Surgery is possible during all three trimesters. Chemotherapy can be administered in the second and third trimesters without increased risk of foetal malformations. Radiation, endocrine and biological therapies however, must be postponed until after delivery.

Papillary thyroid carcinoma with pleomorphic tumor giant cells in a pregnant woman - a case report.

BACKGROUND: Papillary thyroid carcinoma with pleomorphic tumor giant cells (PTC-PC) is characterized by the occurrence of bizarre, pleomorphic cells within a small area of a conventional PTC. The histologic distinction between PTC-PC and PTC's with a focal anaplastic thyroid cancer (ATC) component (denoted in the 2004 WHO classification as "papillary thyroid carcinoma with spindle and giant cell carcinoma", PTC-SGC) is debated, however the prognosis is thought to be different (excellent for PTC-PC, poor for PTC-SGC). Therefore, this diagnostic challenge is significant for any endocrine pathologist to recognize. Herein, we report the histological and clinical workup of a PTC-PC case, with particular focus on the molecular analyses that facilitated the establishment of the final diagnosis. CASE PRESENTATION: The patient was a pregnant, 28-year-old female presenting with a 30 mm conventional PTC, with focal areas with undifferentiated cells exhibiting exaggerated nuclear pleomorphism. No foci of extrathyroidal extension, angioinvasion or lymph node engagement were seen. Immunohistochemical analyses revealed the pleomorphic cells exhibiting retained differentiation. Molecular genetic analyses demonstrated a codon V600 missense mutation of the BRAF gene, but no TP53 or TERT promoter mutations. The absence of an aggressive phenotype in addition to the lack of mutations in two major ATC-related genes led to the diagnosis of a PTC-PC. Postoperative MRI showed no evidence of metastatic disease. Radioiodine ablation was performed seven months post-operatively, and a SPECT-CT imaging did not show signs of residual tissue. She is well and without signs of disease 16 months post-operatively. CONCLUSIONS: PTC-PC is a differential diagnosis to PTC-SGC that mandates careful considerations. Taken together with previous publications, PTC-PC seems to be histologically similar to PTC-SGC, but clinically distinct. Even so, the distinction is not easily made given the different therapeutic consequences for each individual patient. This is the first report that includes molecular genetics to aid in finalizing the diagnosis. Exclusion of mutations in TP53 and the TERT promoter could be considered as an adjunct tool when assessing papillary thyroid cancer with focal pleomorphism.

Management of Skull Base Tumors in the Obstetric Population: A Case Series.

BACKGROUND: Neoplasms rarely present during pregnancy; however, increases in plasma volume, hormone release-induced growth, and tumor hypervascularity can cause rapidly progressive symptoms of varying severity, ranging from those not requiring intervention to those necessitating emergent operations. Here we describe an algorithm for the management of symptomatic neoplasms in the obstetric population and provide recommendations for surgical indications and timing. METHODS: Patients who presented to the skull base clinic at a large tertiary care hospital between 2010 and 2016 were reviewed to identify those who presented with a skull base tumor during pregnancy. RESULTS: Our study cohort comprised 9 women with a skull base tumor during pregnancy. Four patients presented with symptoms that necessitated emergent skull base surgery, and 5 underwent surgery after delivery or were followed with continued surveillance. All operated patients had a World Health Organization grade I or II meningioma or schwannoma. There were no maternal complications. Based on our experience with this cohort, we have created a management algorithm. CONCLUSIONS: Management of a symptomatic tumor during pregnancy requires balancing the potential for curing the mother and the risk of harming the fetus. Trimester of pregnancy is the most critical factor in evaluating the need for urgent management. The second trimester is the optimal time for surgery, associated with the lowest risk for spontaneous abortion or preterm birth. The first and third trimesters are associated with increased risk of miscarriage and preterm labor, respectively. Induction of labor for preterm delivery, followed by surgery, may be appropriate in the early third trimester. Regardless of the perceived risk, however, all pregnant women with an emergent presentation should be offered surgery, regardless of trimester.

Maternal and obstetrical outcome in 35 cases of well-differentiated thyroid carcinoma during pregnancy.

OBJECTIVES/HYPOTHESIS: Thyroid cancer, with 6% to 10% of cancer diagnoses, is one of the most common malignancies during pregnancy. Its treatment poses a risk for the pregnancy, as the thyroid gland plays a crucial role in the evolution of pregnancy. The aim of this study is to evaluate treatment of primary well-differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes. STUDY DESIGN: This is an international cohort study. METHODS: Primary thyroid cancer patients were identified from the database of the International Network on Cancer, Infertility, and Pregnancy registration study. Data on histopathological characteristics, diagnostic and therapeutic interventions, outcome (obstetrical, neonatal, and maternal) and maternal follow-up were analyzed. RESULTS: Thirty-five patients with well-differentiated thyroid carcinoma were eligible. All 35 patients underwent surgery, 29 (83%) of which during pregnancy. Procedures during pregnancy were mainly total thyroidectomies (n = 24). The median number of days between diagnosis and surgical treatment was different between the groups with surgery during and after pregnancy (27 vs. 139 days, P < .001). Both maternal and neonatal outcomes were uncomplicated, regardless of gestational age during surgery. CONCLUSIONS: Well-differentiated thyroid carcinoma diagnosed during pregnancy has a favorable outcome for both mother and child. Surgical management during pregnancy has no negative impact on the pregnancy regardless of the trimester at the time of surgery. However, the potential negative effects of thyroid surgery early in pregnancy demand management of these patients in an experienced multidisciplinary team to provide the best possible care for these patients and their unborn babies. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1493-1500, 2018.

Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast.

Breast cancer is the most common cancer and the leading cause of cancer death among women. Despite all efforts, about 11,939 deaths and 50,000 new diagnoses for breast cancer were estimated among Italian women in 2016. Therefore new approaches are needed to improve the survival and higher remission rates. We present a case of a woman with carcinoma of the breast and multiple metastases after right mastectomy, axillary dissection, repeated cycles of chemo and radiotherapy, and estrogen block. Biological method formulated by Prof. L. Di Bella (DBM) produced a complete and stable objective response without toxicity. The DBM includes antiproliferative molecules, such as somatostatin, prolactin and estrogen inhibitors together with differentiating and apoptotic molecules such as melatonin (MLT), Retinoids, Vitamin E, D3, Vit. C, Calcium, Amino sugars, associated with metronomic microdoses of chemotherapy drugs. The blood tests did not show any damage but a progressive reduction of Prolactin, Estradiol, and IGF1, and continuing low levels of GH. The objective result of this case, in the absence of toxicity, demonstrates the efficacy of the treatment and is in agreement with the positive results already published on the use of the DBM. Not requiring hospital or day hospital admission, and with no significant toxicity, the DBM avoided the significant side effects of chemo- and radiotherapy. We believe that this case can encourage more interest and more in-depth studies on the possibilities that have been opened up in oncology by the DBM treatment of the metastatic breast cancer.

Monte Carlo Simulation of Radiotherapy for Breast Cancer in Pregnant Patients: How to Reduce the Radiation Dose and Risks to Fetus?

This study estimated the fetal dose and risks from radiotherapy for breast cancer with 6 MV X-rays. Breast irradiation was simulated with the MCNP code using two mathematical phantoms corresponding to patients in the early and middle periods of pregnancy. Monte Carlo simulations were performed to determine the appropriate fetal shielding. For a 50-Gy tumor dose, the unshielded fetal dose reached up to 133.1 mGy. Fetal protection with a lead shield of dimensions 30 × 30 × 5 cm3 placed besides the treatment couch resulted in maximum doses of 22.0 and 70.3 mGy at the first and second trimesters of gestation, respectively. These shielded fetal doses may be associated with a fatal cancer risk during childhood up to 0.42% and a maximum probability for the appearance of heritable effects of 0.17%. The use of fetal shielding ensures the absence of deterministic effects from radiotherapy during the first 24 weeks of gestation.