Bilateral Cancer Research Articles

Clinicopathologic characteristics of incidental thyroid carcinoma in euthyroid patients receiving total thyroidectomy for multinodular goiter: A retrospective cohort study.

Total thyroidectomy is the treatment of choice for multinodular goiter (MNG). In some of these cases, incidental thyroid cancer (ITC) is detected postoperatively. Papillary thyroid microcarcinoma (PTMC), the most common type of ITC, has clinical factors and pathologic similarities with ITC that have not been well clarified previously. We investigated the incidence and characteristics of ITC and PTMC in euthyroid patients undergoing total thyroidectomy for MNG. We retrospectively investigated the data of 151 euthyroid patients who underwent total thyroidectomy for MNG between January 2016 and December 2020. Patients with PTMC were then selected from among those with ITC for further data analysis. The incidence rates of ITC and PTMC were 31.1% (47/151) and 21.1% (32/151), respectively. The mean age of patients with ITC was 52.8 ± 11.7 years, which was younger than that of patients with benign MNG (57.2 ± 12.5 years, p < 0.05). Bilateral cancer was observed in 17 patients with ITC (17/47, 36.2%) and nine with PTMC (9/32, 28.1%). The numbers of patients in the ITC and PTMC groups whose cancer was not on the side comprising the dominant tumor were 15 (15/47, 31.9%) and 13 (13/32, 40.6%), respectively. The multivariate analysis demonstrated that younger age was a clinical factor associated with ITC and PTMC. Younger age is a clinical factor for ITC and PTMC. We recommend taking considering clinical factors and pathologic characteristics of ITC and PTC when considering total thyroidectomy in euthyroid patients with MNG.

Multi-detector CT chest: can it omit the further need for contrast enhnaced spectral mammography in breast cancer patients candidate for CT staging?

BackgroundDuring multi-detector computed tomography (MDCT) of the chest, incidental breast lesions (IBLs) are occasionally encountered. Mammography remains the gold standard for the early detection of breast cancer. However, limitations exist in patients with dense breasts. Contrast spectral mammography (CESM) is widely available compared to MRI; it increases the sensitivity for breast cancer detection without decreasing the specificity.ResultsThe study is a prospective study that included 113 female breast cancer patients for CT staging. One hundred and six of the patients had unilateral carcinoma and 7 of them had bilateral cancer with a total of 120 breasts evaluated. The CT findings were correlated with CESM findings regarding the multiplicity and bilaterality of the disease. The sensitivity, specificity, PPV, NPV, and accuracy of the CT in the detection of multiplicity were 97.44%, 100%, 100%, 95.45%, and 98.33%, respectively, and the sensitivity, specificity, PPV, NPV, and accuracy of the CT in the detection of bilateral disease were 68.18%, 97.96%, 88.24%, 93.20%, and 92.50%, respectively.ConclusionsBreast cancer patients for MDCT chest as a part of their metastatic workup can omit the further need for CESM.

Sequential bronchoplastic upper lobectomy as a surgical component of multimodal treatment for synchronous bilateral multiple primary non-small cell lung cancer

Relevance. Lung cancer (LC) is the leading cause of cancer-related death worldwide including Russia. Surgery remains the standard of care for early non-small cell lung cancer (NSCLC). However, as the disease progresses, the risk of metastasis increases, and the effectiveness of surgical intervention decreases. The treatment strategy for patients presenting with a single NSCLC has long been developed. However, for patients with two or more tumors, especially in both lungs, the correct choice is determined by many additional factors. Currently, the view on the surgical treatment for synchronous multiple primary NSCLC has changed dramatically. However, patients with locally advanced synchronous NSCLC often receive conservative treatment, and for those who do undergo surgery, the prognostic factors are unclear. The disease prognosis in patients after surgical treatment for bilateral synchronous multiple primary NSCLC has now been proven to be favorable. Pneumonectomy is believed to have no any negative effect on survival; however, several authors reported on a 1.5-2-fold increase in postoperative mortality in a series of surgeries for synchronous NSCLC. Case description. We herein report a case in which extended bronchoplastic upper lobectomy was successfully applied in the treatment of a patient with bilateral synchronous NSCLC. Our experience demonstrates that the sequential application of modern therapeutic modalities results in satisfactory long-term outcomes in the treatment of locally advanced LC.Conclusion. Due to its uniqueness, this clinical case will be useful for developing treatment strategy for synchronous locally advanced NSCLC as well as for improving the quality of life of patients and increasing their survival.

Abstract 2497: Inherited copy number variants that increase risk of developing pediatric germ cell tumors with a particular focus on the X chromosome

Abstract Pediatric malignant germ cell tumors (GCTs) are heterogeneous but are grouped together due to the presumed common cell of origin, the primordial germ cell (PGC). Little is known about etiology; however, evidence supporting in utero origins of pediatric and adult GCT suggests that disruptions in normal germ cell development are likely to be highly relevant. Germline copy number variants (CNVs) are a plausible source of inherited genetic variation and have not been thoroughly evaluated to date. CNVs on the X chromosome are of particular interest because individuals with both Klinefelter syndrome (47, XXY) and Turner syndrome (45, X) are at increased risk of pediatric GCT, suggesting that alterations in X chromosome dosage contribute to etiology. A family study of adult testicular cancer where at least one member had bilateral cancer identified a significant linkage peak at Xq27 (hLOD=4.7). In addition, somatic copy number gains of chromosome X are frequently seen in adult testicular germ cell tumors. Given these findings in adult GCT, similar aberrations may also be relevant risk factors for the pediatric group. Pediatric GCT samples were obtained from a Children’s Oncology Group study and state biobank programs in Michigan and California. Genotyping array data were generated using the Illumina HumanCoreExome Beadchip (Illumina, San Diego). CNV calls were made for 2,002 GCT cases and 1,402 controls with high quality intensity data using Genvisis, which has specialized algorithms to make CNV calls on the X chromosome. Klinefelter syndrome cases (n=27) were excluded from the analyses. No study sample had classic Turner syndrome; however, one female case had a giant 51Mb deletion of Xq. Analyses were performed for females-only, males-only, and everyone together. We identified two regions that are study-wide significant on chromosome X at Xq27.1 and Xp11.2 and one nominally significant near Xq28. The most significant finding was identified in females-only and is located within a region that encodes genes within the SPANX family. Evidence suggests these genes affect germ cells; however, supporting data is reported in spermatozoa rather than oocytes. The events in our study were large (240kb), had similar breakpoints, and appear to be flanked by repetitive DNA that might lead to recurrent events at the same region. The variant was present in the control samples within gnomAD at a low allele frequency (0.18%). In our study, both deletions and duplications were noted: 11 female cases (1 or 2 expected based on gnomAD allele frequencies) and 0 female controls (0-1 expected). The finding was not replicated in males (6 male cases and 5 male controls harbored similar CNVs). We are in the process of validating these in silico and potentially via quantitative PCR. Findings may shed light on disruptions in normal development that may increase risk of GCT. Citation Format: Shannon S. Cigan, John J. Meredith, John Zaharick, Erica Langer, Anthony J. Hooten, John A. Lane, Nathan Pankratz, Jenny N. Poynter. Inherited copy number variants that increase risk of developing pediatric germ cell tumors with a particular focus on the X chromosome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2497.

Optimized detection of germ cell neoplasia insitu in contralateral biopsy reduces the risk of second testis cancer.

To evaluate whether optimized and standardized diagnostic procedures would improve detection of germ cell neoplasia insitu (GCNIS) in the contralateral testis of patients with testicular germ cell tumour (TGCT) and decrease the rate of metachronous tumours, which in a nationwide Danish study was estimated to be 1.9%. This was a retrospective analysis of outcomes in 655 patients with TGCT who underwent contralateral biopsies (1996-2007) compared with those in 459 non-biopsied TGCT controls (1984-1988). The biopsies were performed using a standardized procedure with immunohistochemical GCNIS markers and assessed by experienced evaluators. Initial histopathology reports were reviewed, and pathology and survival data were retrieved from national Danish registers. In 604/608 patients diagnosed as GCNIS-negative (four were lost to follow-up), the cumulative incidence of metachronous TGCT was estimated in a competing risk setting using the Grey method. All cases of metachronous TGCT were re-examined using immunohistochemistry. Germ cell neoplasia insitu was found in 47/655 biopsied patients (7.2%, 95% confidence interval [CI] 5.4-9.5%). During the follow-up period (median 17.3 years) five of the 604 GCNIS-negative patients developed a TGCT. In 1/5 false-negative biopsies, GCNIS was found on histological revision using immunohistochemistry and 2/5 biopsies were inadequate because of too small size. The estimated cumulative incidence rate of second tumour after 20 years of follow-up was 0.95% (95% CI 0.10%-1.8%) compared with 2.9% (95% CI 1.3%-4.4%) among the non-biopsied TGCT patients (P = 0.012). The estimates should be viewed with caution due to the small number of patients with metachronous TGCT. Optimized diagnostic procedures improved the detection rate of GCNIS in patients with TGCT and minimized their risk of developing metachronous bilateral cancer. Urologists should be aware of the importance of careful tissue excision (to avoid mechanical compression) and the need of adequate biopsy size. Performing contralateral biopsies is beneficial for patients' care and should be offered as a part of their management.

Impact of Endocrine Therapy Adherence on Outcomes in Elderly Women with Early-Stage Breast Cancer Undergoing Lumpectomy Without Radiotherapy.

National Comprehensive Center Network guidelines recommend radiotherapy (RT) omission in women age ≥ 70 years with estrogen receptor-positive (ER+), cN0, T1 tumors post-lumpectomy if they receive endocrine therapy (ET). However, little is known about the impact of poor adherence on locoregional recurrence (LRR) in elderly women forgoing RT. Women age ≥ 70 years with pT1-2 ER+ breast cancer undergoing lumpectomy without RT from 2004 to 2019 were identified from a prospectively maintained database. ET adherence, calculated as treatment duration over follow-up time up to 5 years, was determined by chart review. We compared clinicopathologic characteristics and rates of LRR between women with high adherence (≥ 80%), low adherence (< 80%), and no ET. Of 968 women (27 bilateral cancers), adherence was high in 676 (70%) and low in 162 (17%); 130 (13%) took no ET. Younger age and use of aromatase inhibitor were associated with high adherence. On multivariable analysis, tumor size (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03-2.68, p = 0.04) and high adherence (HR 0.13, 95% CI 0.07-0.26, p < 0.001) were significantly associated with LRR. At 53 months median follow-up, the 5-year rate of LRR was 3.1% (95% CI 2.4-3.9%) with high adherence, 14.7% (95% CI 11.7-17.7%) with low adherence, and 17.9% (95% CI 13.9-21.8%) with no ET (p < 0.01). Although adherence to ET was high overall, in the 30% of women with low adherence or no ET, LRR rates were significantly increased. Counseling regarding the distinct toxicities of ET and RT can help patients choose the therapy to which they will likely adhere to.

Synchronous bilateral primary ovarian cancer with right endometroid carcinoma and left high-grade serous carcinoma: a case report and literature review

BackgroundEpithelial ovarian cancer is the most frequent gynecologic malignancy; it has a poor prognosis and often occurs bilaterally. Most cases of synchronous bilateral ovarian cancer (SBOC) are metastases from the other ovary, while bilateral primary ovarian cancer is rare.Case presentationThe patient was a 47-year-old Japanese woman with a complaint of abdominal pain for 1 month. Imaging results revealed bilateral ovarian tumors with suspicion of malignancy. The patient underwent a laparotomy with total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and resection of suspected dissemination in the peritoneum. Histopathological and immunohistochemical studies showed that the right ovarian tumor was an endometrioid carcinoma (G2) and had no association with endometriotic lesions. However, the left ovarian tumor was a high-grade serous carcinoma (HGSC). The final staging was stage 1 right endometrioid carcinoma and stage IIb left HGSC. Six courses of adjuvant chemotherapy with paclitaxel, docetaxel, and carboplatin were administered. The patient showed no signs of recurrence 24 months postoperatively.ConclusionsTo the best of our knowledge, the combination of histological types in this case may be the first report of primary bilateral ovarian cancer. In SBOC, it is important to differentiate the subtypes of histology using immunostaining, in addition to morphopathology.

Risk factors for lymph node metastasis of cN0 papillary thyroid carcinoma

Abstract Objective To investigate the risk factors for cervical lymph node metastasis of clinically lymph node-negative (cN0) papillary thyroid carcinoma (PTC). Methods Patients and Methods: The clinicopathologic data of patients with cN0 PTC who underwent at least one lobectomy plus central lymph node dissection at Xuzhou Central Hospital from January 2018 to December 2020 were retrospectively collected and the risk factors of lymph node metastasis analyzed. Univariate and multivariate analyses were performed to detect the risk factors for cervical lymph node metastasis. Results A total of 312 patients with cN0 PTC were enrolled in this study. The postoperative pathology results showed that 134 patients (42.9%) had central lymph node metastasis, of whom 24 (17.9%) had lateral lymph node metastasis (LLNM). The univariate analysis results showed that male gender, age &lt;45 years, tumor diameter ≥10 mm, bilateral cancer, capsule invasion, and multiple foci were associated with cervical lymph node metastasis of cN0 PTC (P &lt; 0.05). Further logistic regression analysis results showed that these factors, except age, were independent risk factors for cervical lymph node metastasis of cN0 PTC (P &lt; 0.05). The results also showed that the risk of LLNM increased with an increase in the number of positive central lymph nodes in patients with cN0 PTC (P &lt; 0.05). Conclusion Cervical lymph node metastasis of cN0 PTC is related to many factors, and a high number of positive central lymph nodes indicates a high risk of LLNM. Patients with risk factors should undergo preventive central lymph node dissection at the first surgery, and in patients with a high number of positive central lymph nodes, lateral lymph node dissection should be discreetly performed.

Cancer research collaboration between the UK and the USA: reflections on the 2021 G20 Summit announcement.

On June 10, 2021, the UK and USA released a joint statement about the visit of US President Joe Biden to the G20 Summit at the invitation of UK Prime Minister Boris Johnson. Within this statement (point 18) is the following: “We will convene the first US–UK Bilateral Cancer Summit and bring together researchers, patients, and other stakeholders to share ideas and identify opportunities for collaboration to accelerate advances in lifesaving approaches to cancer, which remains a leading cause of death worldwide.” 1 The White HouseJoint statement on the visit to the United Kingdom of the Honorable Joseph R. Biden, Jr., President of the United States of America at the invitation of the Rt. Hon. Boris Johnson, M.P., the Prime Minister of the United Kingdom of Great Britain and Northern Ireland. https://www.whitehouse.gov/briefing-room/statements-releases/2021/06/10/joint-statement-on-the-visit-to-the-united-kingdom-of-the-honorable-joseph-r-biden-jr-president-of-the-united-states-of-america-at-the-invitation-of-the-rt-hon-boris-johnson-m-p-the-prime-min/Date: June 10, 2021 Date accessed: February 10, 2022 Google Scholar On Nov 10, 2021, the UK Research and Innovation announced that this Summit would take place on Nov 13–14, 2021, “…to identify transformative research grand challenges and ways to resolve barriers to progress in cancer research.” 2 UK Research and Innovation https://www.ukri.org/news/uk-usa-scientific-summit-to-bolster-cancer-research-collaboration/ Google Scholar Information arising from this meeting is scarce, but we know that several different domains from prevention and early detection to exploring social, economic, and environmental factors that contribute to health inequalities were on the agenda.

Preoperative axillary ultrasonography in patients with breast cancer: a prospective study to evaluate its ability to predict axillary tumor load

ObjectiveThis study aimed to determine the ability of axillary ultrasonography to predict the number of lymph nodes with metastases found in sentinel node axillary surgery or axillary lymph node resection in patients recently diagnosed with breast cancer after percutaneous biopsy. MethodsThis prospective study included patients diagnosed with invasive breast cancer by percutaneous biopsy. Axillary lymph nodes were classified at ultrasound examination as suspicious or not suspicious, and the number of suspicious nodes was compared with the number classified as suspicious in the surgical specimen. ResultsWe included 142 patients, 4 of whom had bilateral cancer; 133 of the 146 tumors were clinically classified as T1-T2 N0. The median number of suspicious lymph nodes at ultrasound was 2 (1–6), and the median number of suspicious lymph nodes in the surgical biopsy specimen was 1 (1–16); the difference was not significant (p = 0.1). The correlation between the number of positive lymph nodes on axillary ultrasound and the number of metastatic lymph nodes in the surgical specimen was 72.7% p = 0.0002 and the concordance was 79% (95%CI 62.4%–95.6%) p = 0.0001. For diagnosing high axillary tumor load (≥3 metastatic lymph nodes) versus low axillary tumor load (<3 metastatic lymph nodes), axillary ultrasound had 86.6% sensitivity, 83.3% specificity, 92% PPV, and 71.4% NPV. ConclusionOur results show that preoperative axillary ultrasound can differentiate between low and high tumor load and can be used as a tool to select the type of treatment. These results need to be confirmed in randomized multicenter studies.

Utility of dual-energy contrast-enhanced spectral mammography for the diagnosis of multicentric breast cancer

Background. Breast cancer (BC) can be unifocal, multifocal, multicentric (MCBC) and bilateral according to number and localization of tumors. MCBC has different clinical and biological characteristics compared to unifocal BC, for example, a higher risk of lymph node involvement, a more aggressive natural history and a worse prognosis. Therefore, accurate diagnosis and detection of MCBC is one of the main tasks of imaging.Objective: to compare diagnostic accuracy of contrast enhanced spectral mammography (CESM) and digital mammography (DM) in the diagnosis of MCBC.Materials and methods. The study included 438 women with suspected BC. The results of DM and CESM were compared with the results of a pathomorphological study performed after surgery or biopsy to assess the effectiveness of imaging modalities. DM was performed for all women using a Senographe DS (GE, USA) unit. CESM was performed after intravenous injection of non-ionic contrast agents using injector with breast compression in the craniocaudal and mediolateral projections. The study was performed for both glands regardless of the location of the suspicious lesion in order to timely diagnose clinically asymptomatic bilateral cancer. The final diagnosis was made based on the results of the pathomorphological examination. MCBC was diagnosed when two or more tumors at a distance of 3 cm or more from each other were detected. Visualization of additional grouped calcifications of malignant type occupying a small portion of breast tissue (more than 15 pieces per 1 sq. cm) was considered as another mammographic sign of MCBC.Results. According to the pathomorphological examination BC was diagnosed in 154 (35 %) women out of 438 examined patients. MCBC was identified in 25 (16 %) of 154 patients. CESM was more effective than DM in detecting MCBC with sensitivity of 88.0 % vs 48.0 % (p = 0.002), accuracy of 92.2 % vs 90.9 %, negative predictive value of 97.6 % vs 90.8 % (p = 0.02), respectively. But the specificity was significantly higher in DM than in CESM – 99.2 % vs 93.0 % (p = 0.009), respectively, and the positive predictive value did not differ significantly (p = 0.12).Conclusion. CESM is a more sensitive method for diagnosing MCBC compared to DM with sensitivity of 88.0 % vs 48.0 %. The high negative predictive value of CESM (97.6 %) confirms the fact that this modality is an effective method for planning surgery and radiation therapy.

Transmanubrial approach with thoracoscopic surgery for bilateral lung cancer: a case report

Transmanubrial approach with thoracoscopic surgery for bilateral lung cancer: a case report

First experience of superselective embolization of renal arteries supplying the tumor with subsequent laparoscopic kidney resection

Background. Patients with signs of tumor lesions in a single kidney or in the only one functioning kidney, with bilateral renal tumors are at high risk of functional failure or insufficiency of the kidney after surgery. Joint discussions with specialists in X-ray endovascular surgeries resulted in the development of a treatment algorithm for patients with localized kidney cancer who require organ-sparing surgery without ischemic kidney resection.Objective: to evaluation of the immediate results of two-stage surgical treatment of localized kidney cancer in patients with signs of tumor lesions in a single kidney or in the only one functioning kidney, with bilateral renal tumors, including superselective embolization of the artery supplying the tumor at the first stage, and laparoscopic kidney resection without renal ischemia parenchyma at the second stage.Materials and methods. This study included 5 patients with localized kidney cancer, who underwent two-stage treatment at Moscow Regional Oncology Dispensary between 24.03.2021 and 19.04.2021. The first stage included superselective embolization of the artery supplying the tumor; the second stage implied laparoscopic kidney resection 6-7 days following the first stage.Results. The median age of the patients was 62 years (range: 42-73 years). Four patients (80%) had unilateral kidney lesions, while 1 patient (20 %) had bilateral (synchronous) kidney cancer. The mean RENAL score was 8 (range: 6-10); patients were distributed as follows: score 4-6 in 40 %, score 7-9 in 40 %, and score &gt;10 in 20 % of patients. At the first stage, patients underwent endovascular embolization of the branches of the renal artery. Patients had superselective embolization of either middle (n = 3; 60 %), upper (n = 1; 20 %), or lower (n = 1; 20 %) segmental arteries supplying the tumor. In one of them (20 %), we identified 3 large arterial branches; in another one (20 %), we identified 2 large arterial branches.At the second stage, we performed laparoscopic kidney resection. None of the patients required renal artery clamping, because there was an excellent visualization of the demarcation zone and no significant blood loss. The resection area was sutured in 1 case (20 %). In 2 individuals (40 %), a hemostatic sponge was installed in the removed tumor bed. In the remaining 2 cases (40 %), hemostasis was ensured by coagulation. The median blood loss was 100 mL (range: 50-200 mL). The postoperative period was uneventful in all patients. None of the patients developed symptoms of acute renal failure.Conclusion. Thus, superselective embolization of arteries supplying a kidney tumor has undeniable advantages in organ-sparing surgeries for patients with localized kidney cancer and some additional kidney problems, when organ preservation is crucial for patient's life.

Occult Synchronous Bilateral Fallopian Tube Cancers: Hysterectomy and Bilateral Salpingectomy for a Benign Indication

Occult Synchronous Bilateral Fallopian Tube Cancers: Hysterectomy and Bilateral Salpingectomy for a Benign Indication

114 The Use of Magnetic Resonance Imaging in Patients with A Post-Operative Diagnosis of Invasive Lobular Carcinoma, A Retrospective Analysis

Abstract Aim Magnetic Resonance Imaging (MRI) is recommended pre-operatively for some patients with invasive breast carcinomas, particularly mammographically occult cancers and when tumour size may affect surgical management. Research has shown a higher incidence of both multifocal (32.7%) and bilateral (7%) cancers in invasive lobular carcinoma (ILC), affecting the surgical management of 27% of cases. The study aim was to identify whether MRI is indicated post-operatively when the pre-operative diagnosis is invasive ductal carcinoma (IDC) but post-operative diagnosis is ILC. Method Retrospective analysis of the medical records of patients with dual coding of IDC and ILC over a five-year period (2014-2019) was conducted. Inclusion criteria included a pre-operative diagnosis of IDC but a post-operative diagnosis of ILC. 167 patients were identified. Results Twenty-nine patients (17%) fulfilled the inclusion criteria. Ten (34%) had MRI scans conducted. Six (21%) were performed pre-operatively, three (10%) post-operatively and one (3%) had both a pre-operative and post-operative scan. None of the post-operative MRI scans showed further disease. One pre-operative scan identified a secondary foci, however the patient still underwent breast conserving surgery. The other nineteen patients received annual mammographic follow-up as per multidisciplinary meeting documentation, with no recurrence to date. Conclusions MRI at our unit is carried out as per NICE guidelines pre-operatively. Our results did not identify any further disease in patients with a post-operative diagnosis of ILC, however the sample size was small. There are currently no guidelines on the use of MRI in these patients and further, larger studies are needed to clarify its role.

Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients

Background The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. Material and methods Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. Results The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5–3.4 Gy, 50 Gy) and 1.1 Gy (0.0–1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3–5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. Conclusion This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.

This Month in Adult Urology

This Month in Adult Urology

Ecografía axilar prequirúrgica en pacientes con cáncer de mama. Estudio prospectivo para valorar la capacidad de predecir la carga tumoral axilar

ObjectiveThis study aimed to determine the ability of axillary ultrasonography to predict the number of lymph nodes with metastases found in sentinel node axillary surgery or axillary lymph node resection in patients recently diagnosed with breast cancer after percutaneous biopsy. MethodsThis prospective study included patients diagnosed with invasive breast cancer by percutaneous biopsy. Axillary lymph nodes were classified at ultrasound examination as suspicious or not suspicious, and the number of suspicious nodes was compared with the number classified as suspicious in the surgical specimen. ResultsWe included 142 patients, 4 of whom had bilateral cancer; 133 of the 146 tumors were clinically classified as T1-T2 N0. The median number of suspicious lymph nodes at ultrasound was 2 (1–6), and the median number of suspicious lymph nodes in the surgical biopsy specimen was 1 (1–16); the difference was not significant (p=0.1). The correlation between the number of positive lymph nodes on axillary ultrasound and the number of metastatic lymph nodes in the surgical specimen was 72.7% p=0.0002 and the concordance was 79% (95%CI 62.4%–95.6%) p=0.0001. For diagnosing high axillary tumor load (≥3 metastatic lymph nodes) versus low axillary tumor load (<3 metastatic lymph nodes), axillary ultrasound had 86.6% sensitivity, 83.3% specificity, 92% PPV, and 71.4% NPV. ConclusionOur results show that preoperative axillary ultrasound can differentiate between low and high tumor load and can be used as a tool to select the type of treatment. These results need to be confirmed in randomized multicenter studies.

Novel folliculin gene mutations in Polish patients with Birt\u2013Hogg\u2013Dub\xe9 syndrome

BackgroundBirt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS.Materials and methodsThe first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations.ResultsBHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41).ConclusionsAll analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

Abstract 92: Clonal evolution of proliferative lesions into breast cancers

Abstract Introduction: Proliferative lesions in the breast have been implicated in the development of invasive breast cancer. Previous studies showed that adjacent atypical proliferative lesions and breast cancers shared common genetic alterations, suggesting that these evolved from the same ancestral cell. However, the clonal structure of atypical proliferative lesions and their clonal dynamics during progression to cancer are poorly understood. In this study, we compared genetic profiles of proliferative lesions and cancers from the same patients to illustrate the clonal evolution of cancer from a non-malignant epithelial cell. Methods: Multiple samples were collected from various lesions with different disease-level located in the cancer-borne breast, using micro-dissection from formalin-fixed, paraffin-embedded surgical specimens. Somatic mutations and copy number alterations (CNAs) were evaluated by whole exome sequencing. Results: A total of 39 samples from 7 premenopausal females carrying estrogen receptor-positive cancers were analyzed, where the samples were obtained from proliferative lesions (without/with atypia) (N = 3 and 10, respectively), and non-invasive (N = 22) and invasive (N = 4) cancers. The number of somatic mutations per sample increased with disease progression (ranging from 7 to 311). Two cases with bilateral cancers had a pathogenic germline mutation of either BRCA2 or TP53, where no somatic mutations or CNAs were shared by individual proliferative lesions, suggesting multifocal independent cancerous evolutions. By contrast, in the remaining five unilateral cases, no pathogenic germline mutations were detected, but all proliferative lesions, which were separated by a distance of 7 - 70 mm, shared one or more driver alterations, such as an AKT1 mutation, a GATA3 mutation, a CBFB mutation, a PTEN mutation and concurrent 1q gain and 16q loss, while harboring private mutations/CNAs of their own. The analysis of phylogenic trees based on the number of shared mutations predicted an early origin of these founder mutations, which frequently predated decades before the onset of cancer. Conclusions: Our results suggest that early breast cancer development is shaped by the evolution of multiple precancerous clones. In hereditary cases, this process is thought to be substantially promoted multi-focally within the entire breasts, due to innate genomic instability in each mammary epithelial cell for pathogenic germline mutations. By contrast, in sporadic cases, the ancestral cell which has acquired a founder genetic alteration expands macroscopically long before the onset of cancer. These expanded clones work as the niche predisposed to additional mutations, in which branching evolution occurs multi-focally and raises up multiple proliferative lesions, from which invasive cancer finally evolves. Our findings provide unique insight into the early development of breast cancer. Citation Format: Tomomi Nishimura, Nobuyuki Kakiuchi, Kenichi Yoshida, Yasuhide Takeuchi, Hirona Maeda, Yusuke Shiozawa, Masahiro M. Nakagawa, Yotaro Ochi, Yukiko Kawata, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa. Clonal evolution of proliferative lesions into breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 92.