Assisted Reproductive Technology without Embryo Discarding or Freezing in Women ≥40 Years: A 5-Year Retrospective Study at a Single Center in Italy.

The protocols commonly used in assisted reproductive technology (ART) consist of long-term embryo culture up to the blastocyst stage after the insemination of all mature oocytes, the freezing of all the embryos produced, and their subsequent transfer one by one. These practices, along with preimplantation genetic testing, although developed to improve the live birth rate (LBR) and reduce the risk of multiple pregnancies, are drawing attention to the possible increase in obstetric and perinatal risks, and adverse epigenetic consequences in offspring. Furthermore, ethical-legal concerns are growing regarding the increase in cryopreservation and storage of frozen embryos. In an attempt to reduce the risk associated with prolonged embryo culture and avoid embryo storage, we have chosen to inseminate a limited number of oocytes not exceeding the number of embryos to be transferred, after two days or less of culture. We retrospectively analyzed 245 ICSI cycles performed in 184 infertile couples with a female partner aged ≥40 from January 2016 to July 2021. The results showed a fertilization rate of 95.7%, a miscarriage rate of 48.9%, and a LBR of 10% with twin pregnancies of 16.7%. The cumulative LBR in our group of couples was 13%. No embryos were frozen. In conclusion, these results suggest that oocyte selection and embryo transfer at the cleaving stage constitute a practice that has a LBR comparable to that of the more commonly used protocols in older women who have reduced ovarian reserve.

Signet ring cell component predicts the response to neoadjuvant chemoradiotherapy in rectal cancer. Long interim results of a single institution experience.

There are limited studies evaluating the correlation between the presence of signet ring carcinoma and tumor response to neoadjuvant therapy in the rectum. Hereby, we aimed to report for the first time our experience from Upper Egypt through assessing the predictive role of signet ring cell component (SRCC) in the response to preoperative chemoradiotherapy (PCRT) and the impact of histological types (SRCC versus other types) on survival. This retrospective study analysed the medical records of 195 patients with locally advanced rectal cancer treated from 2011, to 2018. Patients were divided into two groups according to histological types: SRCC group and non SRCC group. All patients received PCRT followed by surgery. SRCC group was associated with significant higher rate of complete clinical response (cCR) and pathologic complete response (pCR) (83.3% and 88.9% respectively) as compared to non SRCC group (9.0% and 10.2% respectively); P<0.0001. Fifteen cases (93.8%) who were diagnosed by magnetic resonance tumor regression grade (mrTRG) and diffusion weighted imaging (DWI) as cCR after PCRT, also achieved pCR, in contrast to 88.9% of cases without SRCC. Signet ring histology was the only predictor of pCR in multivariate analysis (P=0.027). There was no statistically significant difference between both histological groups as regard to survival. SRCC is an important predictor of pCR and assessing their response to PCRT using mrTRG and DWI showed high sensitivity for the detection of cCR, making them good candidates for watch-and-wait approach. Histological types did not significantly affect the survival outcome.

The efficacy and safety of extended adjuvant temozolomide following concurrent radio-chemotherapy among Egyptian patients with newly diagnosed glioblastoma multiforme.

Although concurrent radio-chemotherapy and adjuvant temozolomide (TMZ) treatment for 6 cycles has been established as a standard of care for newly diagnosed glioblastoma multiforme (GBM) patients, the recommended duration of adjuvant TMZ remains a matter of debate. Hereby, we aimed to report for the first time our experience from Upper Egypt through comparing survival and toxicity profile between two treatment modalities of adjuvant TMZ (> six cycles versus six cycles) and delineating factors of prognostic significance in Egyptian patients with newly diagnosed GBM treated by radiation therapy with concomitant and adjuvant TMZ. Between June 2016 and February 2018, the medical records of 121 patients were eligible to be retrospectively reviewed to extract the study relevant data. All patients received concurrent radio-chemotherapy, followed by TMZ for 6 cycles in 29 patients (Group 1) and for >6 cycles in 26 patients (Group 2). Patients in Group 1 had a median PFS of 15 months (95% CI: 10.215-19.785), while those in Group 2 had a median PFS of 18 months (95% CI: 16.611-19.389). After a median follow up duration of 20 months (range: 12-41), the median OS was 18 months (95% CI: 13.420-22.580) in Group 1 and 22 months (95% CI: 18.777-25.223) in Group 2. There was no statistically significant correlation between the number of chemotherapy cycles and PFS (P=0.513) or OS (P=0.867). The extent of surgical resection was the only independent prognostic factor for both PFS (P=0.015) and OS (P=0.028) by multivariate analysis. Three grade ≥3 hematologic toxicity were encountered in 3 patients. One in the six-cycle group (neutropenia), and two in the extended cycles group (one had neutropenia and the other one developed thrombocytopenia). No statistically significant difference in the toxicity profile between both groups. The results of our study suggest that extended TMZ therapy is safe and tolerable, however it did not significantly improve PFS or OS as compared to the standard six-cycle course. Larger randomized studies are required to shed more light on this issue.

Does a Very Short Length of Abstinence Improve Assisted Reproductive Technique Outcomes in Infertile Patients with Severe Oligo-Asthenozoospermia?

In recent years, a growing number of studies seem to support the beneficial effects of a very short abstinence period on sperm parameters, especially in patients with oligo-asthenozoospermia (OA). On this basis, the aim of this study was to evaluate the effects of a short period of abstinence (1 h) on intracytoplasmic sperm injection (ICSI) outcomes in infertile patients with severe OA. We performed a retrospective study on 313 ICSI cycles in which couples were divided into two different groups based on sperm parameters of the male partners. Group 1 included normozoospermic men or male partners with a mild OA (n = 223). Group 2 included male partners with severe OA (n = 90). They were asked to provide a second consecutive ejaculation after 1 h from the first one. The best ejaculate was used to perform ICSI. We found a significant increase of total (p < 0.001) and progressive motility (p < 0.001) in the second ejaculate of patients of Group 2 compared with those of the first one. Spermatozoa of the second ejaculate were chosen for ICSI for all patients in Group 2. We found statistically significant improvement of clinical pregnancy rate (p = 0.001) and embryo quality (p = 0.003) in couples in Group 2 compared to those of Group 1. No statistically significant difference was found in fertilization, implantation, live birth delivery, and miscarriage rates between the two groups. Therefore, a second semen sample collected after a very short time-interval in patients with severe OA allowed us to obtain significantly higher clinical pregnancy rate with improved embryo quality compared to normozoospermic men or patients with mild OA. Fertilization, implantation, live birth delivery, and miscarriage rates were similar between the two groups. The present study shows that a second consecutive ejaculate could represent a simple strategy to obtain better sperm parameters and assisted reproductive technology (ART) outcomes in infertile patients with mild-severe OA.

Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab.

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non-small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single-agent nivolumab. All patients with mNSCLC and mRCC who received nivolumab at the Department of Oncology, Prince Sultan Military Medical City (Riyadh, Saudi Arabia) between November 2016 and April 2018 were identified. The records of patients who developed oligometastatic disease progression during nivolumab treatment and were subsequently treated with RT, with nivolumab continued beyond disease progression, were retrospectively reviewed. Details of RT, clinical outcomes and toxicity data were collected. Of the 96 patients who received nivolumab, 22 received multiple courses of RT. A total of 39 sites were irradiated: Bone (n=15), lung (n=9), brain (n=8), adrenal gland (n=2), renal bed (n=2), skin (n=1), ethmoid sinus (n=1) and scalp (n=1). Partial response and complete response were noted at 25 (64%) and 3 (8%) sites, respectively. Stable disease was noted at 6 sites (15%) and disease progression was noted at 5 sites (13%). The median time on nivolumab from the date of the first fraction of RT was 4.5 months (range, 1.5-29 months) for patients with mNSCLC and 5 months (range, 1-38.5 months) for patients with mRCC. No patients developed grade 3-4 toxicities. Grade 2 pneumonitis was noted in 3 patients receiving lung RT. The addition of RT appeared to initiate a response and prolong the duration of nivolumab treatment. Therefore, the combination of nivolumab and RT was found to be well tolerated, with response rates exceeding those in published studies of nivolumab monotherapy.

Atypical diffuse bilateral cystic lung changes secondary to erlotinib treatment in a patient with metastatic non-small cell lung carcinoma: A case report and literature review.

Erlotinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients with sensitizing epidermal growth factor receptor (EGFR) mutations. The response rate to erlotinib is ~60% and the incidence of erlotinib-induced interstitial lung disease (ILD) is ~1-4%. The Response Evaluation Criteria in Solid Tumours (RECIST) tool is commonly used to assess response to erlotinib; however, evaluation of response and subsequent progression in the presence of atypical cystic lung changes may be challenging. We herein present a rare case of diffuse cystic lung changes secondary to erlotinib treatment in a patient with EGFR mutation-positive metastatic NSCLC. Challenges in assessing atypical tumour response to erlotinib, pitfalls in using RECIST and differential diagnosis of TKI-related ILD are discussed in detail.

Efficacy of Nivolumab in a Patient with Metastatic Renal Cell Carcinoma and End-Stage Renal Disease on Dialysis: Case Report and Literature Review.

Treatment of patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD) on dialysis poses a therapeutic challenge, particularly as this patient group was excluded from the pivotal clinical trials. In addition, there is uncertainty regarding drug dosing/pharmacokinetics, lack of safety and efficacy data, and potential for increased toxicity when using targeted therapy or immunotherapy for the management of patients with mRCC on dialysis. Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor antibody, is indicated for the treatment of patients with mRCC who have received prior antiangiogenic therapy. Given the above-mentioned uncertainties, clinicians may be reluctant to use nivolumab for this patient population, leading to potential denial of life-prolonging medications. We report the case of a 72-year-old gentleman with mRCC and ESRD on dialysis who received second-line nivolumab therapy and achieved an excellent symptomatic and radiological response, remaining progression-free for over 22 months. In addition, we have reviewed the pharmacokinetic data and published retrospective case studies to review the management options for patients with mRCC and ESRD on dialysis.

Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review.

Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity.

Rare Case of Intracardiac Renal Cell Carcinoma Metastasis with Response to Nivolumab: Case Report and Literature Review.

Intracardiac metastases in the absence of inferior vena cava involvement is a rare occurrence in patients with metastatic renal cell carcinoma (mRCC). There is limited evidence regarding the efficacy and safety of standard treatment modalities for mRCC patients with intracardiac metastases. Presence of intracardiac metastases is known to indicate poor prognosis and may potentially increase risk of treatment-related complications. Recent advances in RCC management have integrated nivolumab, a programmed death-1 (PD-1) receptor inhibitor, as a preferred treatment option in the second-line setting after failure of prior anti-angiogenic therapy; or in combination with ipilimumab, an anti-Cytotoxic T-lymphocyte antigen-4 antibody as first-line therapy for intermediate to poor risk patients with mRCC. The efficacy and toxicity of nivolumab in patients with mRCC and intracardiac metastases has never been reported previously. We herein present the first reported case of mRCC with intracardiac metastasis and a resultant excellent response to nivolumab treatment and discuss the imaging techniques and treatment options for this rare presentation.

Using Natural Language Processing to Extract Abnormal Results From Cancer Screening Reports.

OBJECTIVES: Numerous studies show that follow-up of abnormal cancer screening results, such as mammography and Papanicolaou (Pap) smears, is frequently not performed in a timely manner. A contributing factor is that abnormal results may go unrecognized because they are buried in free-text documents in electronic medical records (EMRs), and, as a result, patients are lost to follow-up. By identifying abnormal results from free-text reports in EMRs and generating alerts to clinicians, natural language processing (NLP) technology has the potential for improving patient care. The goal of the current study was to evaluate the performance of NLP software for extracting abnormal results from free-text mammography and Pap smear reports stored in an EMR. METHODS: A sample of 421 and 500 free-text mammography and Pap reports, respectively, were manually reviewed by a physician, and the results were categorized for each report. We tested the performance of NLP to extract results from the reports. The 2 assessments (criterion standard versus NLP) were compared to determine the precision, recall, and accuracy of NLP. RESULTS: When NLP was compared with manual review for mammography reports, the results were as follows: precision, 98% (96%-99%); recall, 100% (98%-100%); and accuracy, 98% (96%-99%). For Pap smear reports, the precision, recall, and accuracy of NLP were all 100%. CONCLUSIONS: Our study developed NLP models that accurately extract abnormal results from mammography and Pap smear reports. Plans include using NLP technology to generate real-time alerts and reminders for providers to facilitate timely follow-up of abnormal results.

Parotid gland sparing with helical tomotherapy in head-and-neck cancer.

PURPOSE: This study evaluated the ability of helical tomotherapy to spare the function of the parotid glands in patients with head-and-neck cancer by analyzing dose-volume histograms, salivary gland scintigraphy, and quality of life assessment. METHODS AND MATERIALS: Data from 76 consecutive patients treated with helical tomotherapy (Hi-Art Tomotherapy) at the University Hospital Brussel were analyzed. During planning, priority was given to planning target volume (PTV) coverage: ≥ 95% of the dose must be delivered to ≥ 95% of the PTV. Elective nodal regions received 54 Gy (1.8 Gy/fraction). A dose of 70.5 Gy (2.35 Gy/fraction) was prescribed to the primary tumor and pathologic lymph nodes (simultaneous integrated boost scheme). Objective scoring of salivary excretion was performed by salivary gland scintigraphy. Subjective scoring of salivary gland function was evaluated by the European Organization for Research and Treatment of Cancer quality of life questionnaires Quality of Life Questionnaire-C30 (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35 (H&N35). RESULTS: Analysis of dose-volume histograms (DVHs) showed excellent coverage of the PTV. The volume of PTV receiving 95% of the prescribed dose (V95%) was 99.4 (range, 96.3-99.9). DVH analysis of parotid gland showed a median value of the mean parotid dose of 32.1 Gy (range, 17.5-70.3 Gy). The median parotid volume receiving a dose <26 Gy was 51.2%. Quality of life evaluation demonstrated an initial deterioration of almost all scales and items in QLQ-C30 and QLQ-H&N35. Most items improved in time, and some reached baseline values 18 months after treatment. CONCLUSION: DVH analysis, scintigraphic evaluation of parotid function, and quality of life assessment of our patient group showed that helical tomotherapy makes it possible to preserve parotid gland function without compromising disease control. We recommend mean parotid doses of <34 Gy and doses <26 Gy to a maximum 47% of the parotid volume as planning goals. Intensity-modulated radiotherapy should be considered as standard treatment in patients with head-and-neck cancer.

Can 18-FDG-PET during radiotherapy replace post-therapy scanning for detection/demonstration of tumor response in head-and-neck cancer?

PURPOSE: In routine practice, the tumor response in head-and-neck cancer (HNC) is assessed 3-4 months after radiotherapy (RT). We compared the results of fluorodeoxyglucose-positron emission tomography (FDG-PET) during (47 Gy) and 4 months after RT. METHODS AND MATERIALS: In 40 patients with HNC, PET was performed before (PET1), at the end of Week 4 (47 Gy) (PET2), and 4 months after RT (PET3). Visual analysis classified patients as having a complete response (CR) or a non-CR (NCR). The sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for PET2 and PET3 were determined. The 2-year overall survival (OS) rate for a CR and NCR was calculated for both response evaluation points. RESULTS: After a median follow-up of 26 months, 10 patients had died, 6 had residual disease, and 24 remained disease free. The overall sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of PET2 vs. PET3 for the detection of a CR was 28.6%, 81.8%, 31.0%, 80.0%, and 42.5% vs. 78.6%, 75.0%, 60.0%, 88.0%, and 77.5%, respectively. The 2-year OS rate determined at 47 Gy was 90.0% and 71.8% for a CR and NCR, respectively, and did not appear to be significantly different (p = .50). For the study, at 4 months, the OS was significantly better in the CR group (91.8%) than in the NCR group (49.9%; p = .0055). CONCLUSION: The high specificity and positive predictive value for the evaluation of tumor response with PET2 and PET3 might avoid unnecessary salvage surgery in patients with a CR. In contrast to PET3, the sensitivity of PET 2 was low, and the difference in OS between the CR and NCR groups was not significantly different. Therefore, the evaluation of the tumor response with FDG-PET at 4 months after RT completion cannot be replaced by FDG-PET during RT at 47 Gy.

Pattern of failure after helical tomotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: Helical tomotherapy (HT, Hi-Art TomoTherapy(®)) is a recently developed radiation device delivering highly conformal dose with a rotational gantry resulting in more uniform target doses and better avoidance of organs at risk. Treatment failure patterns in head and neck cancer (HNC) patients treated with HT were analyzed. PATIENTS AND METHODS: 63 patients with a biopsy-proven HNC were treated with HT. In patients with locoregional failure, the volume of failure (Vf) was contoured and co-registered with the initial planning computed tomography scan. With the use of dose-volume histogram (DVH) analysis, the Vf was classified as "in-field" (InF), "marginal" (MF) or "outside-field" (OutF), if ≥ 95%, 20-94%, and < 20% of Vf, respectively, were within the 95% isodose. RESULTS: Median follow-up time was 25 months (95% confidence interval 19.4-28 months). 2-year overall survival, disease-free survival, and locoregional control were 66%, 54%, and 77%, respectively. 13 patients developed a locoregional failure (four local, eight regional, and one local and regional). After DVH analysis, there were ten InF and two MF recurrences as well as one OutF recurrence. CONCLUSION: Target delineation and coverage were adequate. The majority of locoregional failures were InF, i.e., in the high-dose region. Future work on dose escalation to the highest risk regions is recommended.

Can 18F-FDG-PET response during radiotherapy be used as a predictive factor for the outcome of head and neck cancer patients?

OBJECTIVES: We investigated if (18F) fluoro-2-deoxy-D-glucose positron emission tomography (F-FDG-PET) during radiotherapy or concurrent chemoradiotherapy adds information about the treatment outcome compared with an FDG-PET study before treatment. METHODS: Forty-three patients with head and neck cancer were treated with helical tomotherapy. F-FDG-PET was performed at baseline and during the treatment after 47 Gy. Tracer accumulation at the tumor site was assessed visually and semiquantitatively using the maximal standardized uptake values (SUV(max)). With median SUV(max) of both the studies as cutoff, patients were categorized into low and high SUV(max) groups. For visual analysis, two independent observers classified patients as complete metabolic responders (CMR) or noncomplete metabolic responders (NCMR). RESULTS: At baseline the median SUV(max) was 8.11 (2.41-15.13). The overall survival (OS) and disease-free survival (DFS) were 81 and 67% versus 50 and 40% for the low and high SUV(max), respectively. OS was significantly different (P=0.027). During therapy, median SUV(max) was 4.03 (1.94-7.58). OS and DFS were 82 and 63%, versus 47 and 42% for the low and high SUV(max) group, respectively. OS was significantly different (P=0.026). No significant differences between CMR versus NCMR in OS (72 vs. 60%), and DFS (56 vs. 49%) were found. CONCLUSION: Categorizing patients on the basis of a semiquantitative approach resulted in significant differences in OS for both the scans before and during therapy. Future work on a larger number of patients is warranted to determine SUV(max) cutoff values which could be used for the early identification of patients with poor treatment outcome or perhaps other therapeutic approaches.

The use of the modified hypo-osmotic swelling test for the selection of immotile testicular spermatozoa in patients treated with ICSI: a randomized controlled study.

BACKGROUND: Various methods for the selection of viable sperm from among immotile testicular spermatozoa for use in ICSI have been described in non-randomized studies. We have conducted a randomized controlled study to compare the use of the modified hypo-osmotic swelling (HOS) test (50% culture medium + 50% Milli-Q grade water) with that of sperm selection on the basis of their morphology alone. METHODS: A total of 79 couples with immotile testicular spermatozoa treated with ICSI were randomly assigned into two groups. In the first group, spermatozoa used for injection were selected using the modified HOS test, while in the second group spermatozoa were selected on the basis of their morphology. RESULTS: The fertilization rate was significantly higher in the HOS test group (43.6%) compared with the no-HOS test group (28.2%) [odds ratio (OR) 2.494; 95% confidence interval (CI) 1.606-3.872]. The pregnancy and ongoing pregnancy rates were also higher in the HOS test group (27.3% versus 20.5%) compared with the no-HOS test group (5.7% versus 2.9%) (OR 6.188, 95% CI 1.282-29.860; and OR 8.743, 95% CI 1.050-72.783, respectively). CONCLUSIONS: The use of the modified HOS test for the selection of viable sperm from among immotile testicular spermatozoa for ICSI results in higher fertilization, pregnancy and ongoing pregnancy rates compared with morphological selection.

Sperm velocity and morphology, female characteristics, and the hypo-osmotic swelling test as predictors of fertilization potential: experience from the IVF model.

OBJECTIVE: To determine, among the following variables, the predictors of sperm fertilization potential of a given semen sample: sperm count, eight sperm velocity characteristics determined by computer-assisted semen analysis, the sperm morphology score determined by strict criteria, and the hypo-osmotic swelling (HOS) test, using the IVF model. DESIGN: Data from 58 couples attending the assisted conception unit for conventional IVF treatment were analyzed retrospectively by simple linear regression and multiple stepwise regression analysis, taking the fertilization rate as the dependent factor. RESULTS: The mean sperm velocity and the strict sperm morphology assessment were the only parameters showing significant correlation with the fertilization rate. A minimum sperm velocity of 13 microm/s and a minimum strict sperm morphology of 2% were necessary to achieve fertilization in 50% of the oocytes. The results of the HOS test did not correlate with the fertilization rate. An equation was devised to calculate the expected fertilization rate based on the mean sperm velocity and the strict morphology score, and can be used to counsel patients prior to assisted conception. CONCLUSIONS: The mean sperm velocity and strict sperm morphology evaluation are good predictors of fertilization potential, but the HOS test is not.