Negative Nodes Research Articles

Sentinel lymph node biopsy in patients with breast cancer. Experience in implementing at the regional level. Priority issues

Background. Despite the fact that sentinel lymph node biopsy (SLNB) in breast cancer patients has become a routine diagnostic procedure, it is still of great interest to researchers, since the priority issues of choosing methodology, equipment, technology, and stages of use are still being discussed. Although all obstacles to this technique implementation into routine clinical practice have been eliminated, SLNB in locally advanced breast cancer is still rarely used. We describe the experience of implementing SLNB in Nizhny Novgorod Regional Clinical Oncology Dispensary. We also discuss organizational, tactical, and practical approaches aimed to minimize the number of errors in technical terms, as well as to choose a multidisciplinary approach to the development of regulations for the examination and treatment of patients with locally advanced breast cancer.Aim. To assess the efficacy of SLNB implementation for patients with locally advanced breast cancer at the regional level.Materials and methods. This study included 500 patients with invasive (T1–2) breast cancer with clinically negative sentinel lymph nodes of all immunohistochemical subtypes that had undergone SLNB and histological examination. Sentinel lymph nodes were visualized using the radioisotope colloid 99mTc-Nanotop. We present the implementation algorithm for this procedure into routine clinical practice and evaluate short-term results.Results. A total of 500 patients have undergone SLNB. The first 30 cases were considered pilot cases, where all patients positive for sentinel lymph nodes additionally underwent standard axillary lymph node dissection. We observed a 100 % concordance of histological results. Then the surgery was routinely performed for all patients from this category. The assessment of short-term surgical outcomes demonstrated significant improvement of the postoperative period, reduced frequency of postoperative complications (persistent seroma of the axillary area to 2.85 %), reduced length of hospital stay (by 52.7 %) and improved functional and aesthetic results in the majority (>62 %) of patients.Conclusion. Our algorithm of SLNB use in patients with breast cancer in routine clinical practice at the regional level allows for rapid method implementation, reduced length of hospital stay, better functional and aesthetic results, and lower incidence of persistent seroma of the axillary area.

Association between NDRG1 protein expression and aggressive features of breast cancer: a systematic review and meta-analysis

BackgroundN-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.MethodsThe protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.ResultsA total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13–1.05, I2: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32–(-0.20), I2: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).ConclusionThe study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.

Using MammaPrint on core needle biopsy to guide the need for axillary staging during breast surgery

BackgroundAt present, the only opportunity to omit axillary staging is with Choosing Wisely criteria for women ages >70 y with cT1 2N0 estrogen receptor–positive/human epidermal growth factor receptor 2–negative breast cancer. However, many women are diagnosed when pathologic node status–negative, raising the question of additional opportunities to omit sentinel lymph node biopsy. We sought to investigate the association between MammaPrint, a genomic test that estimates estrogen receptor–positive breast cancer recurrence risk, and pathologic node status, with the aim that low-risk MammaPrint could be considered for omission of sentinel lymph node biopsy if associated with pathologic node status–negative. MethodsA single-institution database was queried for all women with cT1 2N0 estrogen receptor–positive/human epidermal growth factor receptor 2–negative invasive breast cancer with breast surgery as their first treatment and MammaPrint performed from 2020 to 2021. Patient and tumor factors, including MammaPrint score, were compared with axillary node status for correlation. ResultsA total of 668 women met inclusion criteria, with a median age of 66 y. MammaPrint was low-risk luminal A in 481 (72%) and high-risk luminal B in 187 (28%). At the time of breast surgery, 588 (88%) had sentinel lymph node biopsy, 27 (4%) had axillary lymph node dissection, and 53 (7.9%) had no axillary staging. Most women in both the pathologic node status–negative and pathologic node status–positive cohorts had low-risk MammaPrint (355 [73.3%] pathologic node status–negative vs 91 [69.5%] pathologic node status–positive), and women with low-risk MammaPrint did not have a significantly lower risk of pathologic node status–positive (P = .377). ConclusionLow-risk MammaPrint does not predict lower risk of pathologic node status–positive breast cancer. Based on our results, genomic testing does not appear to provide additional personalization for the ability to omit sentinel lymph node biopsy for patients outside of the Choosing Wisely guidelines.

Is therapeutic lymph node dissection of value for lymph node recurrence in melanoma?

BackgroundTherapeutic lymphadenectomy (TLND) is still performed in most melanoma patients to treat nodal recurrences after initial negative lymph node biopsy (-SLNB), despite the lack of evidence for survival benefit. We sought to compare melanoma-specific survival (MSS) and distant metastasis-free survival (DMFS) of patients who underwent TLND versus no TLND using our institutional and MSTL-1 databases. MethodsWe identified 146 patients with nodal recurrence following -SLNB: 132 underwent TLND and 14 did not. DMFS and MSS were evaluated for the cohorts followed by a matched-pair analysis between the cohorts. ResultsNo difference was observed in five-year DMFS (p ​= ​0.454) and five-year MSS (p ​= ​0.945) between the two groups. The matched-pair analysis showed similar results (p ​= ​0.329 and p ​= ​0.363 for DMSF and MSS, respectively). ConclusionsFrom this limited retrospective study, TLND for nodal recurrence after a -SLNB does not appear to improve DMFS or MSS in melanoma patients compared to no TLND.

Fine-needle aspiration biopsy of axillary lymph nodes: Areliable diagnostic tool for breast cancer staging.

Pathologic evaluation of sentinel lymph node biopsy (SLNB) samples is crucial for axillary staging in patients newly diagnosed with breast cancer. Patients with pathologic evidence of nodal metastasis scheduled for upfront surgery typically also undergo axillary lymph node dissection (ALND). Although SLNB is the gold standard method for detecting nodal metastasis, axillary lymph node fine-needle aspiration biopsy (FNAB) utility has not been thoroughly explored. Ultrasound-guided axillary lymph node FNAB samples along with concurrent ipsilateral breast tissue samples were searched and reviewed. The control group included histologic findings of axillary dissection or intraoperative SLNB results. A total of 354 axillary lymph node FNAB samples with matched histology were included. Of these, 187 (52.8%) were positive for metastatic carcinoma of breast origin; 143 (40.4%) were negative for metastasis; 12 (3.4%) showed atypical cells; six (1.7%) were suspicious for metastasis; and six (1.7%) were nondiagnostic because of a lack of lymphoid tissue and malignant cells. Of the 143 negative FNAB samples, 22 (15.4%) were positive on either intraoperative SLNB or ALND. When only the positive and negative FNAB samples were accounted for (n=330; 93.2%), overall diagnostic sensitivity and specificity were 89.4% and 99.2%, respectively. Although axillary SLNB is the standard procedure for detecting nodal metastasis of breast origin, axillary lymph node FNAB appears to be a suitable alternative in a significant proportion of patients. A standard SLNB should be performed in cases of negative axillary lymph node FNAB findings, particularly nodes with abnormal imaging findings.

Colloid and pigmented histiocytes in lymph node aspirates as a clue to metastasis in patients with a history of papillary thyroid carcinoma.

Cystic changes, calcification, colloid material, and multinucleated giant cells are frequently associated with primary and metastatic papillary thyroid carcinoma (PTC). These features are sometimes present in negative lymph node fine-needle aspiration cytology (FNAC). This study aims to review nodal aspirates of PTC to elucidate the significance of these cytological features in aspirates without tumor cells. FNAC specimens from patients with PTC confirmed on thyroidectomy were reviewed for cystic changes, tumor-associated features, and lymphoid components. Histologic follow-up of the lymph nodes were retrieved for correlation. A total of 113 aspirates were retrieved, of which 79 showed tumor cells on the FNAC specimen, and 95 were matched to a positive lymph node histology. At univariable analysis, calcification (n = 18/113, p = .044), colloid material (n = 40/113, p = .001), multinucleated giant cells (n = 29/113, p = .028), tumor cells (n = 79/133, p < .001), foamy histiocytes (n = 36/113, p = .002) and pigmented histiocytes (n = 62/113, p < .001) were associated with a positive histology. Presence of lymphoid fragments (n = 11/113, p < .001) and abundant background lymphocytes correlated with a negative histologic follow-up (n = 45/113, p = .005). In aspirates without tumor cells, multivariable analysis demonstrated colloid material (p < .001) and pigmented histiocytes (p = .003) to be independently predictive of metastatic PTC, whereas lymphoid fragments (p < .001) were independently associated with a negative histologic follow up. Colloid material and pigmented histiocytes, and to lesser degree calcification and multinucleated giant cells, when seen in an aspirate without tumor cells, raises suspicion metastatic disease. On the contrary, the lymphoid fragments can be regarded as supportive evidence of adequate sampling and a true negative result.

Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes.

Patients receiving neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) typically show better survival outcomes than those undergoing immediate surgery for muscle-invasive bladder cancer. However, most studies have not considered the lymph node (LN) status when evaluating NAC's survival benefits. This study sought to delineate the impact of NAC on patients based on their pathologically determined LN status at the time of RC. We examined data from 1395 patients treated at two departments between 1991 and 2022. Of them, 481 had positive LNs. A comparison of overall survival (OS) outcomes revealed that patients without LN involvement ((y)pN0) benefited from NAC with a hazard ratio (HR) of 0.692 (95% confidence interval [CI] 0.524-0.915). In contrast, patients with (y)pN+ showed no improvement with NAC (HR 0.927, 95%CI 0.713-1.205). Notably, patients treated with NAC for stage <ypT2ypN+ tumours experienced reduced OS compared to their counterparts who did not receive NAC. The HR was 3.111 (95%CI 1.249-7.746). Given that persistent nodal disease after NAC correlates with a worse prognosis, additional post-operative treatments should be considered.

The expression of matrix metalloproteinase 2, 9 and 11 in Ethiopian breast cancer patients

IntroductionMatrix metalloproteinases (MMPs) play a pathophysiological role in cancer initiation and progression. Numerous studies have examined an association between MMP-2, MMP-9, and MMP-11 expression and clinicopathological characteristics of breast cancer (BC); however, no research has been done on the MMP expression levels in BC cases from Ethiopia.Materials and methodsA total of 58 formalin-fixed paraffin-embedded breast tissue samples encompassing 16 benign breast tumors and 42 BC were collected. The RNA was extracted and quantitative reverse-transcription PCR was performed. GraphPad Prism version 8.0.0 was used for statistical analysis.ResultsThe MMP-11 expression levels were significantly higher in breast cancer cases than in benign breast tumors (P = 0.012). Additionally, BC cases with positive lymph nodes and ER-positive receptors had higher MMP-11, MMP-9, and MMP-2 expression than cases with negative lymph nodes and ER-negative, respectively. The MMP-11 and MMP-9 expressions were higher in grade III and luminal A-like tumors than in grade I-II and other subtypes, respectively.ConclusionThe MMP-11 expression was higher in BC than in benign breast tumors. Additionally, MMP-11, MMP-9, and MMP-2 were higher in BC with positive lymph nodes and estrogen receptors. Our findings suggest an important impact of MMPs in BC pathophysiology, particularly MMP-11.

SAT337 Maternal Cell free DNA Testing Reveals Incidental Finding Of Adrenocortical Carcinoma

Abstract Disclosure: F. Akanbi: None. S. Raja: None. T. Else: None. Maternal Cell-free DNA Testing Reveals Incidental Adrenocortical Carcinoma IntroductionAdrenocortical carcinoma (ACC) is rare; with 1 to 2 cases per million. It is unclear if ACC in pregnancy represents a specific association though 150 cases have been reported. We report a case of ACC detected during fetal sex determination using cell free DNA (cfDNA). Case Report: A 30 year old G1P0 woman presented at GA of 25 weeks with results of non-invasive prenatal screening (NIPS) done for fetal sex determination, which noted atypical findings concerning for possible maternal neoplasm. Pregnancy had been uncomplicated; she had no significant past medical history or features of hypercortisolism. Family history was positive for lung and prostate cancer. Physical examination revealed healthy looking female with no Cushingoid facies, abdomen matched stated GA. Full body MRI revealed 5.5 cm right adrenal mass with lymph nodes metastases. CT-guided retroperitoneal lymph node biopsy showed ACC.She was asymptomatic with significantly elevated urine free cortisol 3648 (3.5-45 mcg/24 hour), serum cortisol 67.5 (5-25 ug/dl), 11-deoxycortisol 3910 (10-79 ng/dl), and suppressed ACTH &amp;lt;5 (5-52 pg/ml). Electrolytes were normal, DHEAS 342 (35-430 ug/dl), aldosterone &amp;lt; 3 (4-31 ng/dl), renin mass 5 (4-44pg/ml), urinary free normetanephrine 0.23 (&amp;lt; 0.9 nmol/l), urinary free metanephrine &amp;lt; 0.2 (&amp;lt; 0.5 nmol/l). MRI of the chest and brain did not show metastases. She developed at GA 29 weeks, hypertension, proteinuria, and transaminitis. Cesarean section was done at GA 30 weeks followed the next day by right adrenalectomy, IVC repair and retroperitoneal lymph node resection. Pathology showed high-grade adrenal cortical carcinoma (12 cm size) with negative margins, vascular invasion and lymph node involvement (T3, N1, M0), no caval involvement, stage III ACC. During chemotherapy planning, metastases were noted, mitotane and pembrolizumab were initiated, but discontinued after 2 cycles on account of generalized rash and elevated liver enzymes. The tumor progressed on etoposide, doxorubicin and cisplatin (EDP), and second line therapy (gemcitabine and capecitabine) was initiated. Conclusion: Physiologic changes of pregnancy mimic clinical features of ACC and pregnancy associated changes in the HPA axis also make ACC diagnosis challenging. Short fragments of DNA (cfDNA) released into the maternal bloodstream can be detected after 7 weeks of gestation. Approximately 2-20% of total cfDNA is placental, it is used for sex determination and detection of congenital genetic abnormalities, cfDNA can also originate from maternal neoplasms and has been shown to detect lung, breast and colon while case series in patients with ACC showed detection of only 1 out of 3 cases. Surgery remains first line therapy for ACC, but adjuvant therapy, surveillance and hormone replacement are also vital in ACC management. Presentation: Saturday, June 17, 2023

Prediction of negative axillary node clearance by sentinel node-positive to total node ratio: a retrospective cohort study.

Increasing evidence suggests that de-escalation of axillary surgery is safe, without significantly impacting patient outcome. Obtaining positive lymph nodes at a sentinel lymph node biopsy (SNB) can guide decisions toward the requirement of axillary nodal clearance (ANC). However, methods to predict how many further nodes will be positive are not available. This study investigates the feasibility of predicting the likelihood of a negative ANC based on the ratio between positive nodes and the total number of lymph nodes excised at SNB. Retrospective data from January 2017 to March 2022 was collected from electronic medical records. Patients with oestrogen receptor (ER) positive and HER2 negative receptor disease were included in the study. ER-negative and HER2-positive disease was excluded, alongside patients who had chemotherapy before ANC. Of 102 patients, 58.8% (n=60) had no macrometastasis at ANC. On average, 2.76 lymph nodes were removed at SNB. A higher SNB ratio of positive to total nodes [OR 11.09 (CI 95% 2.33-52.72), P=0.002] had a significant association with positive nodes during ANC. SNB ratio less than or equal to 0.33 (1/3) had a specificity of 79.2% in identifying cases that later had a negative completion ANC, with a 95.8% specificity of no further upgrade of nodal staging. A low SNB ratio of less than 0.33 (1/3) has a high specificity in excluding the upgradation of nodal staging on completion of ANC, with a false-negative rate of less than 5%. This may be used to identify patients with a low risk of axillary metastasis, who can avoid ANC.

Contact of the Tumor with the Internal Mammary Perforator Vessels as Risk Factor for Internal Mammary Lymph Node Involvement Based on Dynamic Contrast Enhancing MRI Imaging in Breast Cancer Patients

Distant metastasis free and overall survival of high-risk breast cancer patients can be improved with irradiation of the lymphatic system. However, inclusion of internal mammary region (IMN) markedly increases the dose to the heart. Hence, an estimation of the individual risk of subclinical involvement is necessary in order to balance the oncological benefit versus the cardiac toxicity. In randomized studies the risk stratification for IMN involvement is mainly based on the tumor location (medial, central vs. lateral). The aim of this study was to evaluate whether the contact of the tumor with the internal mammary perforator vessels (IMPV) is an additional risk factor for IMN involvement. For this trial we retrospectively examined 104 sets of pre-treatment dynamic contrast enhanced magnetic resonance imaging (DE-MRI) scans of locally advanced breast cancer patients. All patients had ipsilateral clinical suspect lymph nodes in the axillary region and either positive (n = 52) or negative lymph nodes (n = 52) in the internal mammary region. Based on the DE-MRI we assessed the tumor location as well as contact to the internal mammary perforating vessels (IMPV). Contact between tumor and IMPV was classified into either predominant, minor or no contact. Criteria for a predominant IMPV contact was defined as: main vessel contact or contact to multiple (> = 5) side branches. The tumor location of IMN+ patients were medial in 19.2% (10/52), central in 26.9% (14/52), lateral in 28.8% (15/52) and multicentric in 25.0% (13/52) of. In IMN- patients, tumor location was medial in 9.6% (5/52), central in 26.9% (14/52), lateral in 42.3% (22/52) and multicentric in 21.2% (11/52) in IMN- patients. The tumor size ranged from T1-T4 with most patients staged as T2 (48.1% (IMN+) vs. 38.5% IMN-). Most patients had hormone receptor positive / Her2neu negative disease (36.5% (IMN+) vs. 46.2% (IMN-). 100 % of tumors in IMN+ patients had contact with IMPV: in 94.2% (49/52) criteria for predominant IMPV contact was fulfilled; in the remaining 3 cases (5.8%) the tumor had minor IMPV contact. In IMN- patients however, 36/52 of cases (69.2%) had direct IMPV contact. Predominant contact was found in only 23.1% (12/52), minor IMPV contact in 46.2% (24/52). Predominant contact of the tumor with IMPV appears to be a potential risk factor for IMN involvement in breast cancer patients and could be used for stratification for IMN-irradiation in future trials.

The Feasibility of Level Ib Sparing Intensity Modulated Radiation Therapy in Nasopharyngeal Carcinoma Patients with High-Risk Factors: Based on International Guideline

In spite of the rarity of level Ib recurrence after intensity-modulated radiation therapy, the International Guideline (IG) provides the risk factors for prophylactic coverage. In practice, however, there are significant differences between institutions. The purpose of this study is to examine the feasibility of sparing level Ib IMRT in NPC patients with high-risk factors based on IG. From January 2014 to October 2017, newly-diagnostic, non-metastatic NPC patients in our center were retrospectively reviewed. According to the risk factors of prophylactic level Ib coverage in patients with negative level Ib recommended by IG, the characteristics of pre-treatment MRI were analyzed. Four high-risk factors were identified: a. involvement of the structures that drain to level Ib as first echelon (FES), including anterior half of nasal cavity, oral cavity, b. involvement of submandibular gland (SMG), c. with radiologic extranodal extension (rENE) in level II LNs, or d. maximal axial diameter (MAD)≧2 cm in level II LNs. Patients with risk factors were divided into Cohort A (with risk factors a), Cohort B (with risk factor b, but without a), and Cohort C (only with risk factors c and/or d). Recurrence rates of level Ib and regional relapse-free survival (RRFS) rates were evaluated in different cohorts. A total of 961 patients were finally included. Thirty-six cases (3.7%) presented with radiologically positive level Ib metastasis. For the other patients with negative Ib LNs, there were 18, 65, 421, and 444 cases classified as FES involvement, SMG involvement, level II LNs with rENE, and level II nodal with MAD ≧2 cm. Excluding overlap, a total of 571 patients with risk factors were divided into three groups: Cohort A (n = 18), Cohort B (n = 49) and Cohort C (n = 504). Nine patients (9/961, 0.94%) developed level Ib recurrence. Except for 1 patient with positive Ib LNs at diagnosis, 2 did not meet any of the risk factors, while the other six (6/9, 66.7%) met at least one risk factor. The rate of recurrence at neck level Ib was highest in Cohort A (11.1%, 2/18; Ib-sparing group: 0/10, 0.0% vs Ib-covering group: 2/8, 25.0%; P = 0.183). In Cohort B, no cases were found with level Ib recurrence (0.0%, 0/49). In Cohort C, the rates were rare (0.8%, 4/504) in both groups (0.7%, 2/276 vs 0.9%, 2/228; P > 0.999). Among the three Cohorts, there were no significant differences in 5-year RRFS between two groups, which were 90.0% vs 62.5% (p = 0.248), 90.9% vs 92.0% (p = 0.905), and 92.6% vs 90.1% (p = 0.445), respectively. Among patients with high-risk factors, the incidence of grade 3-4 late dry mouth symptom was higher in the level Ib-covering group (3.1% vs 7.5%, P = 0.033). Level Ib sparing appears safe and feasible for NPC patients with negative level Ib LNs, even if combined with risk factors: SMG involvement, and/or level II with rENE, and/or level II MAD ≧2 cm. Level Ib-sparing irradiation reduces dry mouth symptoms compared with level Ib-irradiation.

Early Results of the French Multicenter, Randomized SHARE Trial Comparing Whole Breast Irradiation vs. Accelerated Partial Breast Irradiation in Postmenopausal Women with Early-Stage Breast Cancer

The aim is to report toxicity and cosmetic outcomes at 3 and up to 9 years of follow-up of post-menopausal patients randomized to receive either standard whole breast irradiation (WBI), including hypofractionated options, versus accelerated partial breast irradiation (APBI). From December 2010 to July 2015, 1006 patients were enrolled in 34 French centers. Among the whole population, 28 patients who did not meet the final selection criteria or withdrew consent were excluded leading to a modified intention to treat analysis dataset of 978 patients (WBI: n = 488; APBI: n = 490). Median age (65y) and tumor stage pT1 (99%) rates were similar in both arms. Patients had conservative surgery with clip placement in the tumor bed. Clear margins (> 2mm) were observed in 99% of the patients. In both arms, 96-97% of the patients had negative sentinel lymph node biopsy. The median time interval between surgery and radiotherapy was 57d in WBI vs 62d in APBI. WBI schedules consisted of 50 Gy in 25 fr+16 Gy (n = 212) or 40 Gy in 15 fr (n = 156) or 42.5 Gy in 16 fr (n = 120). APBI arm consisted of 38.5 Gy or 40 Gy in 10 fr, 2 fr/day. Overall, 94 patients from the APBI arm finally received standard WBI. For statistical considerations, SHARE trial, sponsored by UNICANCER (NCT01247233) is a non-inferiority randomized controlled trial comparing APBI versus WBI in terms of local control as primary objective. Secondary endpoints were severe toxicity (NCI-CTCAE v4 grade ≥ 2), and cosmetic results. For both outcomes, we estimated the cumulative incidences (CI) using Kalbfleish and Prentice method, considering disease relapse, secondary cancer or death as competing events. Treatment effect (APBI vs WBI) was estimated by cause-specific Hazard Ratios (cs-HR) from Cox models. Median follow-up was 5.8y (range, 0.13-9.5). The number of deaths was 27, and the number of local relapses was 8. Among the 978 patients, 582 and 396 had finally WBI and APBI, respectively. The rates of post-operative hematoma, edema and infection were low: 8-9%, 2%, 3-2%, respectively. When considering any type of severe toxicity, we observed a significant reduction rate in APBI compared to WBI: cs-HR = 0.73 (95% confidence interval: 0.61-0.88); p = 0.001, and 3-year CI of severe toxicity at 45% in WBI vs 36% in APBI arm. The difference was also in favor of APBI when considering breast skin toxicity alone: cs-HR = 0.55 (0.44-0.70), p<0.001 and 3-year CI at 36% in WBI vs 21% in APBI arm. Conversely, for breast other toxicities, WBI was found less toxic than APBI with a 3-year CI of 8% vs 15%, respectively. When considering cosmetic results, we observed no significant difference between the two arms in both evaluations by physicians and patients. Historically SHARE is the first APBI trial that included hypofractionated schedules in the standard arm. We report increased risk of severe toxicity and skin breast toxicity in standard arm as compared with APBI arm without any difference in terms of cosmetic results. Longer follow-up is needed.

Prospective Cohort Study to Evaluate Toxicity and Cosmesis between Interstitial APBI and Ultra-Hypo-Fractionated Whole Breast Irradiation in Patients with Early Breast Cancer

Both interstitial multi-catheter brachytherapy based accelerated partial breast irradiation (APBI) and ultra-hypo-fractionated whole breast irradiation (WBI) with 5 fractions can complete treatment in a short time and result in lower treatment-related costs. Although data are available on their toxicity compared with conventional and hypo-fractionated regimens, there are few data directly comparing these two techniques. This prospective cohort study enrolled early breast cancer patients with negative ink margin, T1 or T2 stage, and tumor size of 3 cm or less, with 0 to 3 positive lymph nodes after adequate axillary dissection or negative sentinel lymph node biopsy (N0-1), regardless of receptor status (ER, PR, HER2neu). Of the total 31 patients, 15 received APBI with multi-catheter interstitial brachytherapy (35 Gy in10 fractions over 5 days with a minimum interval of 6 hours between fractions) and 16 patients received WBI (27 Gy in 5 fractions over 5 days) with either 3DCRT or VMAT technique. Acute toxicity was assessed using the RTOG toxicity grading and breast cosmesis was assessed using the Harvard breast cosmesis score. Toxicity and cosmesis were assessed immediately after treatment, after one month, and after three months of treatment. Results were compared between groups using the Mann Whitney U test. All patients completed a 3-month follow-up after completion of treatment. There was no statistically significant difference between the 2 groups in terms of highest grade toxicity (p = 0.97) and acute toxicity immediately after RT (p = 1.0) and after 1 month of RT (p = 0.91). However, at 3 months, more patients in the WBI group had a residual skin reaction than in the APBI group (p = 0.03). There was no statistically significant difference in breast cosmesis scores at any time point. 53.3%, 6.6% had grade 1 and 2 skin toxicities respectively immediately after RT in the APBI group and 62.5% of patients had grade 1 skin toxicity in WBI group. After 1 month 26.6%, 26.6% & 13.3% patients had grade 2, grade 1 and grade 3 toxicities respectively. In the WBI group, at 1 month, 50%, 18.7% and 12.5% patients had grade 1, 3 and 2 skin toxicities respectively. At 3 months, 42.8% and 7.1% of patients in the APBI group had grade 1 and grade 2 toxicities, respectively. In the WBI group, 78.5% and 7.1% of patients had grade 1 and 2 skin toxicities respectively. In this study, no difference in acute toxicity or breast cosmesis was demonstrated between APBI-based interstitial brachytherapy and ultra-hypo-fractionated WBI. Since both regimens can be administered within 5 days, the decision between them is challenging for both physicians and patients. This study can be considered hypothesis-generating and used for further planning of equivalence or noninferiority studies.

Prognostic factor analysis and clinical significance of HER‑2‑positive breast cancers with negative lymph nodes and a tumor diameter ≤1cm.

The 2021 National Comprehensive Cancer Network guidelines recommend that adjuvant chemotherapy combined with trastuzumab be considered for human epidermal growth factor receptor 2 (HER-2)-positive breast cancer patients with small tumors (tumor diameter ≤1 cm) and negative lymph nodes. Additionally, the prognostic factors and clinical significance of HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm remain unclear. In the present study, the clinical data and prognostic factors of 87 patients with HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm admitted to Guangdong Women and Children Hospital from January 2013 to December 2019 were retrospectively analyzed. The median follow-up time was 70 months, the disease-free survival (DFS) of all patients was 94.3% and the overall survival (OS) was 100%. Univariate analysis of prognosis demonstrated that patients aged ≤40 years had significantly lower DFS than those aged >40 (80.8 vs. 100.0%, P<0.001). DFS was significantly improved in patients who were hormone-receptor-positive and patients who received endocrine therapy compared with patients who were estrogen receptor negative and patients who did not receive endocrine therapy (100.0 vs. 89.6%, P=0.039; 100.0 vs. 90.0%, P=0.049). Prognostic univariate analysis demonstrated that patient age, hormone receptor status and use of endocrine therapy were significantly related to the DFS (P<0.05), while none of these were independent factors related to the DFS in the prognostic multivariate analysis (P=0.240, P=0.976 and P=0.925). The proportion of patients with a tumor diameter 0.5-1 cm receiving adjuvant anti-HER-2 treatment was significantly greater compared with patients with tumors with a diameter ≤0.5 cm (46.4 vs. 18.6%, P<0.05). There was no significance difference in the DFS of patients treated with adjuvant chemotherapy with or without anti-HER-2 therapy with tumor diameters ≤0.5 cm (P>0.05), but there was a significant difference in the DFS of patients with a tumor diameter 0.5-1 cm (P<0.05). These results suggested that adjuvant chemotherapy, with or without anti-HER-2 therapy, may affect the prognosis of HER-2-positive breast cancer patients with negative lymph nodes and a tumor diameter of 0.5-1 cm. Therefore, it could be recommended that such patients receive adjuvant chemotherapy and anti-HER-2 therapy in the future.

Reconsidering the Role of Frozen Section in Sentinel Lymph Node Biopsy for Mastectomy Patients

IntroductionAxillary lymph node dissection was recommended for mastectomy patients with more than two nodal metastases from sentinel lymph node biopsy. Conventionally, intraoperative frozen section was sent routinely to reduce the need for second-stage axillary lymph node dissection; however, recent global trend has seen decreasing usage of the intraoperative analyses. This pilot study conducted in Thailand aimed to evaluate the role of intraoperative frozen section of sentinel lymph node biopsy in early-stage breast cancer patients who underwent mastectomy. MethodsA 5-y retrospective study of 1773 patients was conducted in Thailand. The inclusion criteria were early-stage breast cancer patients with either radiologically negative nodes, or radiographically borderline nodes found to be negative on fine needle aspiration who underwent mastectomy and sentinel lymph node biopsy. Reoperations were indicated when three or more nodal metastases were detected on the pathological analysis. The reoperation rate prevented by frozen section and the reoperation rate needed for those with permanent section alone were reported. ResultsAmong 265 patients, 202 patients underwent concomitant intraoperative frozen section while the remaining 63 patients underwent permanent section alone. Six patients (3.0%) from the frozen section group and one patient (1.6%) from the permanent section group were found with more than two nodal metastases. Despite using intraoperative frozen sections, only one patient from each group required reoperation. There was no significant difference in the number of patients requiring reoperation between the frozen section group and the permanent section group. ConclusionsOur study provides strong evidence to all surgeons that in early breast cancer patients undergoing mastectomy, sentinel lymph node biopsy with permanent section analysis alone may not lower the standard of care compared to using additional intraoperative frozen section analysis. Adopting this practice may lead to decreased operation costs, operative time, and anesthetic side effects.

Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.

Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC. Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD). Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC. All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.

Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis

BackgroundSentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy...

Prognostic role of the number of resected and negative lymph nodes in Spanish patients with gastric cancer

IntroductionLymph node (LN) involvement is one of the most critical prognostic factors in resected gastric cancer (GC). Some analyses, mainly conducted in Asian populations, have found that patients with a higher number of total lymph nodes (NTLN) and/or negative lymph nodes (NNLN) have a better prognosis, although other authors have failed to confirm these results. Materials and methodsRetrospective study including all patients with GC resected in a tertiary hospital in Spain between 2001 and 2019 (n = 315). Clinicopathological features were collected and patients were categorized according to the NTLN and the NNLN. Statistical analyses were performed. ResultsMean NNLN was 17. The NNLN was significantly related to multiple clinicopathological variables, including recurrence and tumor-related death. The classification based on the NNLN (N1: ≥16, N2: 8–15, N3: ≤7) effectively stratified the entire cohort into three distinct prognostic groups and maintained its prognostic value within both the pN0 and pN+ patient subsets. Furthermore, it was an independent prognostic indicator for both overall and disease-free survival. Conversely, the mean NTLN was 21.9. Patients with ≤16 LN retrieved exhibited distinct clinicopathological features compared to those with >16 LN, but no significant differences were observed in terms of recurrence or disease-associated death. The application of alternative cut-off points for NTLN (10, 20, 25, 30, and 40) showed no prognostic significance. ConclusionsIn Spanish patients with resected GC the NNLN hold prognostic significance, while the NTLN does not appear to be prognostically significant. Incorporating the NNLN into GC staging may enhance the accuracy of the TNM system.

Effect of known pathological risk factors on the incidence of metastatic lymph nodes and survival in early-stage vulvar cancer: SEER analysis.

The current study was performed to evaluate the incidence of positive lymph nodes (LNs) in relation to known pathological risk factors, specifically among patients with apparent low-grade, small tumors. We used the Surveillance, Epidemiology, and End Results (SEER) database to retrospectively identify patients with vulvar squamous cell carcinoma (SCC) diagnosed between January 1, 2000, and December 31, 2019, with known tumor size and regional LN examined. A comparison between patients who had positive and negative LNs was conducted to identify risk factors for LN metastases in relation to survival. Subgroup analysis was conducted in patients with diagnosed grade 1 vulvar SCC and tumor size up to 2 cm according to the status of LNs. Multivariate analysis found that both grade of disease and tumor size were significant factors in predicting LN status. Among patients with low-grade small tumors up to 2 cm, the odds ratio for positive LNs was 2.5 for those with tumor size larger than 1 cm. In a multivariate survival analysis, older age, larger tumor size, and positive LNs were independently associated with decreased survival. The current study confirms that among small tumors, those larger than 1 cm have a significantly increased risk for positive nodes compared with those smaller than 1 cm, and, among this specific group, patients with positive nodes have decreased survival. Future studies are needed to answer the question of whether, in the era of the sentinel node procedure, it is safe to omit LN evaluation altogether.