T1-T2 N0M0 Research Articles

Nodal Elective Volume Selection and Definition during Radiation Therapy for Early Stage (T1-T2 N0 M0) Perianal Squamous Cell Carcinoma: A Narrative Clinical Review and Critical Appraisal.

Distinction between anal canal and perianal squamous cell carcinomas (pSCCs) is essential, as these two subgroups have different anatomical, histological, and lymphatic drainage features. Early-stage true perianal tumors are very uncommon and have been rarely included in clinical trials. Perianal skin cancers and aCCs are included in the same tumor classification, even though they have different lymphatic drainage features. Furthermore, pSCCs are treated similarly to carcinomas originating from the anal canal. Radiation therapy (RT) is an essential treatment for anal canal tumors. Guidelines do not differentiate between treatment volumes for perianal tumors and anal cancers. So far, in pSCC, no study has considered modulating treatment volume selection according to the stage of the disease. We conducted a narrative literature review to describe the sites at higher risk for microscopic disease in patients with early-stage perianal cancers (T1-T2 N0 M0) to propose a well-thought selection of RT elective volumes.

Disparities in Specialized Radiation Treatment Modalities for Grade Group 2, Intermediate-Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> Men with Grade Group 2 (GG2) intermediate risk (IR) prostate cancer (PCa) have multiple curative radiation (RT) options. Compared to conventional external beam photon RT (XRT), including 3D-conformal RT (3DCRT) and IMRT, highly conformal RT techniques may provide less integral RT dose to normal tissue, including brachytherapy (BT), SBRT, and proton beam radiation therapy (PBT). These treatments require either advanced equipment and/or specialized training. Here we analyzed national trends in utilization of XRT, BT monotherapy, SBRT, and PBT, and assessed potential factors associated with receiving each technique. We hypothesize that socioeconomic and/or racial disparities are associated with differences in utilization of these specialized techniques. <h3>Materials/Methods</h3> Men diagnosed with favorable IR PCa cancer, defined as Gleason 3+4 disease, PSA < 20 and clinical stage T1-T2 N0 M0, between 2004-2017 were identified in the National Cancer Database. Cohorts were defined as: XRT (3DCRT+IMRT, hypofractionated (HF) or standard fractionation (SF)), BT monotherapy (HDR, LDR), SBRT (5 fx) and PBT (HF or SF). Trends in utilization were examined. Associations between technique and patient, clinical disease, and sociodemographic characteristics were assessed by multivariable logistic regression, with <i>P</i><0.05 considered significant. <h3>Results</h3> 71,140 patients met inclusion criteria of which 72.4% received standard XRT and 27.6 % received specialized radiation modalities (18.5% brachytherapy, 6.0% SBRT, & 3.1% PBT). Utilization of XRT and BT declined from 71.0% (XRT) and 27.5% (BT) in 2004 to 69.7% (XRT) and 17.2% (BT) in 2017. Receipt of SBRT and PBT increased from 0% (SBRT) and 1.45% (PBT) in 2004 to 9.9% (SBRT) and 3.3% (PBT) in 2017, respectively. On multivariable logistic regression, Black patients were less likely to receive BT (adjusted OR 0.79; 95%CI 0.74-0.83), SBRT (adjusted OR 0.77; 95%CI 0.70-0.85), or PBT (adjusted OR 0.39; 95%CI 0.33-0.47) compared to XRT (all <i>P</i><0.0001). Socially disadvantaged seniors (SDS; age >65 years with Medicaid insurance) were less likely to receive specialized RT (adjusted OR 0.45; 95%CI 0.31-0.60; P<0.0001). Factors associated with increased likelihood of receiving BT, SBRT, or PBT included: treatment at Academic/Research center, treatment at a metropolitan facility, younger age, lower Charlson-Deyo Comorbidity Score, and lower PSA at presentation (all P < 0.01). <h3>Conclusion</h3> Trends in utilization of RT modalities have dramatically changed in recent years with a sharp decline in BT, a doubling of PBT, and rapid adoption of SBRT, as coded in the NCDB. Compared to White patients with GG2 IR PCa, there are disparities in utilization of BT, SBRT, and PBT for Black patients and for SDS. It is unclear whether similar disparities exist for other prostate cancer grade groups for which BT and SBRT are being utilized. Future efforts should address access-to-care challenges for the use of these specialized techniques as they are expanded into higher GG.

Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer at Facilities With Stereotactic Body Radiation Therapy Programs

<h3>Purpose/Objective(s)</h3> Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT), a less invasive alternative, may facilitate more appropriate patient selection for surgery. <h3>Materials/Methods</h3> An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility's SBRT Experience in years and SBRT-to-Surgery Volume Ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for the associations between facility-level SBRT utilization and post-operative mortality. Interaction testing of independent covariates was performed to assess the effect of SBRT utilization across subgroups. <h3>Results</h3> The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 N0 M0 NSCLC between 2004-2015. The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p < 0.001). During this period, the proportion of facilities that utilized SBRT increased from 4.6% to 77.5% (p < 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p < 0.001). On multivariable analysis, lower 90-day post-operative mortality rates were observed among patients who underwent resection at facilities with greater than six years of SBRT Experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery Volume Ratios above 17% (OR 0.85, CI 0.79-0.92, p < 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that findings were consistent across subgroups. <h3>Conclusion</h3> Patients who underwent surgical resection for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery Volume Ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may improve allocation of patients to surgery or SBRT, particularly for higher-risk patients. The observation of higher post-operative mortality rates at facilities without an SBRT program merits further investigation.

Patients with early-stage (T1-2N0) adenosquamous lung cancer have worse long-term survival compared to patients with early-stage lung adenocarcinoma or squamous cell histology.

8550 Background: Survival outcomes for patients with adenosquamous carcinoma of the lung are not well understood by virtue of reduced prevalence. The objective of this study is to compare the long-term survival among patients with adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma of the lung. Methods: Overall survival of all patients with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma who received guideline-concordant treatment for T1-2N0M0 from 2004-2017 in the National Cancer Data Base was assessed using Kaplan-Meier analysis, multivariable Cox proportional hazard analysis, and propensity score-matched analysis. Results: Among patients who met study criteria (N = 88,983), there were 2,469 (2.77%) patients with adenosquamous, 60,148 (67.59%) with adenocarcinoma and 26,366 (29.63%) with squamous cell carcinoma histology. In patients who had T1-T2 N0 M0 disease, adenosquamous carcinoma was associated with significantly worse 5-year overall survival (58.9% [95%CI:56.6%-61.1%]) when compared with adenocarcinoma (72.4% [95% CI:72.0%-72.8%]) and squamous cell carcinoma (62.6% [95% CI:61.9%-63.3%]). In multivariable Cox proportional hazards analysis, adenocarcinoma (HR 0.81 [95% CI:0.76-0.87], p &lt; 0.001) and squamous cell carcinoma (HR 0.86 [95% CI:0.80-0.92], p &lt; 0.001) continued to be associated with significantly better survival when compared to adenosquamous carcinoma histology. A propensity score-matched analysis of 1,854 adenocarcinoma and 1,854 adenosquamous patients who were well matched by 17 common prognostic covariates (including tumor size and comorbidities) found that adenosquamous histology (57.2% [95% CI:54.7%-59.6%]) was associated with worse survival when compared to adenocarcinoma (63.0% [95% CI:60.6%-65.4%]). An additional propensity score-matched analysis of 1,852 squamous cell carcinoma and 1,852 adenosquamous patients matched by the same covariates demonstrated that adenosquamous carcinoma (57.1% [95%CI:54.6%-59.6%]) was associated with worse survival when compared with squamous cell carcinoma (64.0% [95% CI:61.5%-66.4%]). Conclusions: Early stage adenosquamous carcinoma of the lung is associated with worse overall survival compared to its individual histologic components of adenocarcinoma or squamous cell carcinoma. These observations in both the unmatched and propensity matched patient cohorts invoke consideration of multimodality therapy for these early tumors.

Impact of active surveillance for prostate cancer on the risk of depression and anxiety: Patient-reported outcomes (PROs) from the Vican Prospective Cohort.

220 Background: Active surveillance (AS) is an option for low-risk localized prostate cancer and its use is on the rise due to the good long-term oncologic results. However, its impact on the quality of live of patients, particularly in terms of anxiety and emotional responses related to cancer is poorly evaluated. Methods: The french VICAN cohort is a representative sample of 4174 patients treated for cancer and survivors after 5 years. Patient-reported Outcomes (PROs) were collected prospectively by self-questionnaires on quality of live (SF-12) and treatments side effects. Among the 447 patients with prostate cancer, patients managed by active surveillance (AS), radiotherapy (RT), or radical prostatectomy (RP), for localized T1-T2 N0 M0 cancer with a Gleason score &lt; 8 were selected. Data regarding depressive symptoms and percieved anxiety were analysed comparatively. Results: A total of 301 patients were included, among whom 68 (22.6%) managed by AS, 170 (56.5%) treated by RP and 63 (20.9%) treated with RT. Patients treated with AS had a lower clinical stage (p = 0.04) compared with patients in RP and RT groups. Regarding the impact on the quality of live, there was no significant difference in terms of depressive symptoms (no depressive symptoms reported for 82.4% of patients in the AS group vs 88.8% in RP and 74.6% in RT, p = 0.468) or percieved anxiety (no anxiety reported in 63.3% of cases in the AS group vs 71.2% in RP and 66.6% in RT, p = 0.214). Conclusions: Patients managed by AS for localized prostate cancer do not report more depressive symptoms or anxiety than patients treated with curative treatment (RP or RT). This confirms the importance of offering this therapeutic option if the histopathological criteria allow it and if the patient is compliant.

Patient Selection for Surgery vs Radiotherapy for Early Stage Oropharyngeal Cancer.

Surgery and radiation therapy are both commonly used in the treatment of early stage (AJCC stages T1-T2 N0-M0) oropharyngeal squamous cell carcinoma (OPSCC). Transoral robotic surgery (TORS) and intensity modulated radiation therapy (IMRT) have been reported to result in similar survival and disease control outcomes. However, their side effect profiles widely differ. Nevertheless, patients who experience the worst side effects and quality of life are the ones who receive the combination of TORS and adjuvant radiation or chemoradiation therapy. Thus, appropriate patient selection for surgery to minimize the need for multimodality therapy is key. We propose, in this paper, the use of sentinel lymph node biopsy in the node negative (N0) neck as a means that is worth exploring for selecting patients to either radiation therapy or surgery. Patients with a positive sentinel lymph node (SLN) would be better directed to upfront radiation. On the contrary, patients with a negative SLN biopsy would be more confidently directed towards TORS and neck dissection alone.

Image-guided hypofractionated double-scattering proton therapy in the management of centrally-located early-stage non-small cell lung cancer

Background The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT). Material and methods Between 2009 and 2018, 23 patients with T1–T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58–88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks. Results Median follow-up for all patients was 3.2 years (range, 0.2–9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27–79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46–92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18–61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement. Conclusion Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.

Multivariate analysis of parameters affecting the choice of surgical treatment for patients with localized renal cell carcinoma (RCC)

Objective. To increase the effectiveness of treatment the patients with localized RCC on the basis of determining the main clinical and nephrometric criteria that affect the choice of surgical treatment. Маterials and methods. Results of a retrospective analysis of treatment of 903 patients with localized RCC (T1–T2 N0 M0), which evaluated nephrometric, clinical parameters. Patients are divided into two groups depending on the type of treatment: the group of partial nephrectomy (PN) – 658 patients, the group of radical nephrectomy (RN) – 245. Results. A multivariate analysis of the main clinical, anatomical and nephrometrical criterias by the method of the neural network prediction model found that the most valid indicators affecting the choice of indications for PN or RN was: tumor size, localtion, the volume of functioning renal parenchyma. Nomograms and an electronic calculator developed on this basis make it possible to accurately predict the choice of surgical treatment method for patients (sensitivity 85,5% (95% CI 81,3–89,0%) and specificity 85.5% (95% CI 82,3–88,3%)). Conclusion. In case of polar and lateral location of RCC, the indication for PN was the volume of functioning renal parenchyma of more than 58% and 67%, respectively. In case of hilar location of RCC, the main indication for PN was the tumor size of less than 38 mm.

Effect of depth of invasion on lymph node metastasis in early stage

Introduction: Lip cancer is the most common type of cancer in the oral cavity. It occurs in the lower lip at a rate of 90%–95%, and among lower lip tumors, squamous cell carcinoma (SCC) is the most common type. Objective: In this study, we investigated the influence of the depth of invasion on the decision for an elective lymph node dissection in cases with early-stage (T1–T2 N0 M0) SCC of the lower lip. Methods: Thirty-two patients that were surgically treated were retrospectively reviewed. Results: Three patients had metastatic lymph node, and their mean depth of invasion was 10.60 mm. Lymph node metastasis significantly increased in tumors with a depth of invasion larger than 5 mm (P = 0.033). Conclusion: The rate of cervical lymph node metastasis increases as the depth of invasion increases.

Quality of life in patients, suffering localized reno-cellular cancer after operative treatment

Objective. To rise the efficacy of treatment in patients, suffering localized reno-cellular cancer (LRCC), studying quality of life in patients and determination of optimal procedure of operative treatment. Materials and methods. Of 511 patients, suffering LRCC (T1-T2 N0M0), in whom quality of life was estimated in accordance to the SF-36 questionnaire, renal resection was performed in 422 (82.6%), nephrectomy - 89 (17.4%). The observation duration median have constituted 28.9 mo (from 3 to 131 mo). Results. A patient’s cognition of the oncological disease missing have raised the quality of life self-estimation, predominantly in accordance to indices of psychological component of health after nephrectomy and after renal resection. Comparing the quality of life between the patients’ groups, there was obtained a statistically significant advantage of renal resection over nephrectomy in accordance to five indices of quality of life, including: physical functioning - 75 [65; 85] points after nephrectomy and 80 [70; 90] points after renal resection (p &lt; 0.005); general state of health - 65 [57; 72] and 70 [65; 80] (p &lt; 0.001); vital activity - 65 [55; 70] and 70 [60; 75] (p &lt; 0.005); psychological health - 76 [60; 80] and 80 [68; 88] (p &lt; 0.005); the emotionally-role functioning - 66.7 [66.7; 100] and 100 [66,7; 100] (p &lt; 0.05) points, accordingly. Conclusion. Renal resection has a statistically proven advantage over nephrectomy in accordance to patients’ quality of life, determined, basing on data from the SF-36 questionnaire, predominantly due to better psychological self estimation of the patient’s state of health (p &lt; 0.01). Difference between the investigated groups in accordance to indices of pain intensity, social and physical-role functioning was not established.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

The necessity of IIb dissection in T1\u2013T2N0M0 oral squamous cell carcinoma: protocol for a randomized controlled trial

BackgroundThere is a growing debate on the relationship between health-related quality of life (HRQoL) and patient survival which has been going on for the last few decades. The greatest wish of clinicians is to extend the latter while improving the former. Following neck dissection of early-stage oral carcinoma, “shoulder syndrome” appears due to traction of the accessory nerve during removal of level IIb, which greatly affects patient quality of life. Since occult metastasis in level IIb of early-stage oral carcinoma is extremely low, some surgeons suggest that level IIb can be exempt from dissection to improve the HRQoL. However, other surgeons take the opposite view, and thus there is no consensus on the necessity of IIb dissection in T1–2N0M0 oral squamous cell carcinoma (OSCC).MethodsWe designed a parallel-group, randomized, non-inferiority trial that is supported by Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. We will enroll 522 patients with early oral carcinoma who match the inclusion criteria, and compare differences in 3-year overall survival, progression–free survival (PFS) and HRQoL under different interventions (retention or dissection of level IIb). The primary endpoints will be tested by means of two-sided log-rank tests. Analysis of overall and progression-free survival will be performed in subgroups that were defined according to stratification factors with the use of univariate Cox analysis. In addition, we will use post-hoc subgroup analyses on the basis of histological factors that were known to have effects on survival, such as death of invasion of the primary tumor. To evaluate HRQoL, we will choose the Constant–Murley scale to measure shoulder function.DiscussionCurrently, there are no randomized controlled trials with large sample sizes on the necessity of IIB dissection in T1–T2N0M0 OSCC. We designed this noninferiority RCT that combines survival rate and HRQoL to assess the feasibility of IIb neck dissection. The result of this trial may guide clinical practice and change the criteria of how early-stage oral cancer is managed. The balance between survival and HRQoL in this trial is based on early-stage breast cancer treatment and may provide new ideas for other malignancies.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019128. Registered on 26 October 2018.

Utilization of Surgery and Its Impact on Survival in Patients With Early Stage Small-cell Lung Cancer in the United States

IntroductionFor patients with T1 or T2 N0 M0 small-cell lung cancer (SCLC), lobectomy followed by chemotherapy is the standard of care. However, because of its tendency for early dissemination, patients are often treated with concurrent chemo-radiation without surgery. This study was conducted to evaluate the utilization of surgery and its impact on survival in patients with early stage SCLC. Materials and MethodsThe National Cancer Database was queried to identify patients with T1 or T2 N0 M0 SCLC diagnosed from 2004 to 2013. Multivariate logistic regression modeling was utilized to identify factors associated with receipt of surgery. Patients were stratified into 3 groups: chemo-radiation, surgery followed by chemotherapy, and surgery followed by chemotherapy and prophylactic cranial irradiation (PCI). Kaplan-Meier estimators and Cox proportional-hazards regression were used to compare overall survival. Patients were matched on the propensity score. ResultsA total of 3879 SCLC cases were identified. Of those cases, 80.7% received chemo-radiation. Surgery followed by chemotherapy with or without PCI was associated with better median overall survival (93.0 months [lower 95% confidence interval (CI), 72.5] and 61.7 months [95% CI, 51.8-76.5], respectively) compared with chemo-radiation (31.2 months [95% CI, 26.3-37.0]). PCI offered survival benefit in addition to surgery and chemotherapy (hazard ratio, 0.75). ConclusionsOur study showed a significant survival benefit with surgery (lobectomy or more), adjuvant chemotherapy, and PCI in patients with T1-T2 N0 M0 SCLC.

Radiation to the Immune System May be an Important Risk Factor for Long-term Survival after SBRT in Early Stage Non-small Cell Lung Cancer: A Role of RT Plan Optimization

Stereotactic body radiation therapy (SBRT) is the treatment of choice in patients with early stage inoperable non-small cell lung cancer (NSCLC). Local tumor control after SBRT is outstanding; however, 5-year overall survival rates remain suboptimal at less than 50%, which cannot be fully explained by known etiologies such as comorbidity, distant cancer progression or conventional toxicity. We hypothesize that radiation to normal tissue, particularly the sensitive lymphocytes in the immune system, contribute to the poor survival in these patients. Patients with T1-T2 N0 M0 NSCLC who received SBRT without previous RT and had retrievable radiotherapy (RT) plans in our modern treatment planning system were eligible. The primary endpoint was overall survival, calculated from the start of SBRT. Clinical factors included age, gender, race, tobacco history, respiratory and cardiovascular comorbidity, tumor lobar location, histology, T stage, gross tumor volume (GTV), planning target volume (PTV), and prescription dose BED10. Heart and lung were contoured consistently by one radiation oncologist according to the RTOG atlas. Effective dose to lymphocytes were computed by an in-house model. A total of 280 patients met criteria. The median follow-up was 6.7 years. The median survival time was 33 months (95% CI: 25-42 months). The 2-year, 3-year and 5-year survival rates were 63%, 53% and 45%, respectively. Univariate analysis demonstrated that age (HR=1.02, p=0.04), gender (HR=0.75 for female, p=0.07), tumor T stage (HR=1.3 for T2, 2.5 for T3, using T1 as the reference, p=0.10), KPS(HR=0.97, p<0.001), GTV (HR=1.01, p<0.001), PTV (HR=1.01, p<0.001), mean lung dose (HR=1.2, p<0.001), mean heart dose (HR=1.001, p=0.029) and EDIC were all significantly associated with overall survival. Multivariate analysis demonstrated KPS, GTV, mean lung dose, mean heart dose and EDIC were all significant as continuous variables, but only KPS, GTV, EDIC remained. A 1 Gy increase in EDIC was associated with a 46 % increase in the risk of death, or 20% reduction in 5-year survival. This study is the first to demonstrate that radiation dose to lung, heart and lymphocytes are independent factors predicting long-term overall survival after SBRT. These findings suggests that the poor survival after SBRT is likely at least in part from damage to radiation-sensitive lymphocytes and may suggest an area of further plan optimization during SBRT practice.

Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or Biphasic Mesothelioma?

Benefits of surgical resection for early-stage nonepithelioid malignant pleural mesothelioma (MPM) have not been clearly elucidated. This study investigated whether cancer-directed surgery affects overall survival compared with nonsurgical therapies for T1-T2 N0 M0 sarcomatoid or biphasic MPM patients. Adult patients with clinical stage I or II MPM were identified in the National Cancer Database from 2004 to 2103. Patients who underwent cancer-directed surgery were matched by propensity score with patients who had received chemotherapy/radiotherapy or no treatments. Overall survival was compared using a Cox proportional hazard regression model. From National Cancer Database queries, 878 patients with clinical stage I or II MPM with sarcomatoid (n= 524) or biphasic (n= 354) histology were identified. Overall median survival was 5.5 months for patients with sarcomatoid mesothelioma. The cancer-directed surgery improved overall survival compared with no operation (median survival, 7.56 months vs 4.21 months, respectively; p < 0.01). In the biphasic group, median overall survival was 12.2 months. Again, the cancer-directed surgery improved survival compared with no operation (15.8 months vs 9.3 months, p < 0.01). For both histologies, the cancer-directed surgery improved overall survival compared with those who underwent chemotherapy or radiotherapy, or both, without resection (p < 0.05). Perioperative mortality was 6.0% at 30 days and 21.4% at 90 days. The cancer-directed surgery is associated with improved survival in early-stage MPM patients with nonepithelioid histology compared with those who did not undergo resection or chose medical therapy. Given the high perioperative mortality, a careful patient selection and multidisciplinary evaluation is recommended.

Can axillary node dissection be safely omitted in the elderly? A retrospective study on axillary management of early breast cancer in older women

IntroductionSentinel lymph node biopsy (SLNB) is a minimally invasive technique to stage the axillary lymph node status. The burden of nodal metastasis is of great concern, as the clinical relevance and therapeutic implications of pN1mi and pN0(i+) in the sentinel lymph node (SLN) remain a matter of debate. Materials and methodsWe examined the pathological features of 901 patients above the age of 65 presenting with clinical T1–T2 N0M0 breast tumours (<3 cm), detecting tumours related to llary non-sentinel node (NSN) metastases when the SLN was minimally involved. ResultsA total of 270 patients underwent complete axillary lymph node dissection (cALND) after their SLNB specimen tested positive for macrometastasis, micrometastasis and isolated tumour cells (ITCs). Seventy-six patients were diagnosed with micrometastatic disease pN1mi (27.5%), whilst ITCs (pN0i+) were detected in seven patients (2.5%). NSNs were found to be involved in two patients (2.6%) with micrometastases at the SLN. No further metastatic disease was detected in NSNs when the SLN contained ITCs. At a median follow-up period of 5.8 years, no axillary recurrence was observed among pN1mi and pN0(i+) patients. Lobular histotype, multicentricity and lymphovascular invasion were found to be associated with NSN involvement. DiscussionThe results from our case series are supported by IBCSG 23-01 level 1 evidence, which demonstrated a local recurrence rate of 1% in ‘minimally involved not-surgical treated axilla’. ConclusionsBased on current evidence, we spare well-informed and consenting patients from further axillary surgery when the SLN is minimally involved in early breast cancer within an agreed protocol, whilst scheduling adjuvant treatment based on the patients' primary tumour characteristics.

Planning Target Volume D95 and Mean Dose Should Be Considered for Optimal Local Control for Stereotactic Ablative Radiation Therapy

To identify the optimal dose parameters predictive for local/lobar control after stereotactic ablative radiation therapy (SABR) in early-stage non-small cell lung cancer (NSCLC). This study encompassed a total of 1092 patients (1200 lesions) with NSCLC of clinical stage T1-T2 N0M0 who were treated with SABR of 50Gy in 4 fractions or 70Gy in 10 fractions, depending on tumor location/size, using computed tomography-based heterogeneity corrections and a convolution superposition calculation algorithm. Patients were monitored by chest CT or positron emission tomography/CT and/or biopsy after SABR. Factors predicting local/lobar recurrence (LR) were determined by competing risk multivariate analysis. Continuous variables were divided into 2 subgroups at cutoff values identified by receiver operating characteristic curves. At a median follow-up time of 31.7months (interquartile range, 14.8-51.3months), the 5-year time to local recurrence within the same lobe and overall survival rates were 93.8% and 44.8%, respectively. Total cumulative number of patients experiencing LR was 40 (3.7%), occurring at a median time of 14.4months (range, 4.8-46months). Using multivariate competing risk analysis, independent predictive factors for LR after SABR were minimum biologically effective dose (BED10) to 95% of planning target volume (PTVD95 BED10) ≤86Gy (corresponding to PTV D95 physics dose of 42Gy in 4 fractions or 55Gy in 10 fractions) and gross tumor volume ≥8.3cm(3). The PTVmean BED10 was highly correlated with PTVD95 BED10. In univariate analysis, a cutoff of 130Gy for PTVmean BED10 (corresponding to PTVmean physics dose of 55Gy in 4 fractions or 75Gy in 10 fractions) was also significantly associated with LR. In addition to gross tumor volume, higher radiation dose delivered to the PTV predicts for better local/lobar control. We recommend that both PTVD95 BED10 >86Gy and PTVmean BED10 >130Gy should be considered for SABR plan optimization.

Optical coherence tomography in the assessment of oral squamous cell carcinoma resection margins

BackgroundIncomplete surgical removal of cancer is believed to be the main cause of local recurrence and high mortality. This study assessed the use of optical technology (namely optical coherence tomography [OCT]) in examining oral squamous cell carcinoma (OSCC) resection margins to assess if this modality could guide the surgeon during surgical resections. Materials and methodsTwenty-eight T1–T2 N0M0 oral squamous cell carcinoma patients participated in this study. Nineteen patients were males and nine were females. The majority of lesions were in the ventro-lateral tongue, floor of mouth, retromolar trigone and the buccal mucosa.Following tumour resection, the specimen resection margins were optically scanned in the immediate ex vivo phase. Two independent assessors commented on the four resection margins of each specimen. The findings were then compared to the corresponding gold standard histopathology. The average epithelial thickness for both tumor-free and tumor-involved margins was also calculated. ResultsThe pathology reports of the 112 margins revealed 90 tumor-free margins and 22 tumor-involved margins. Examining the data from both senior operating surgeons (assessors), the overall sensitivity and specificity was found to be 81.5% and 87%, respectively. Whilst the positive predictive value was 61.5% and the negative predictive value was 95%. OCT accuracy for the first assessor was 88% and for the second assessor 84%. The assessors’ inter-observer agreement was “very good” for superior, inferior and medial margins; while agreement on the lateral surgical margin status was “good”. Using OCT, the mean epithelial thickness at the tumor-free resection margins was 360μm; while, it was 567μm for the tumour-involved margins. ConclusionOCT is a valuable tool in the assessment of surgical margins. Tumour-involved margins can be identified by architectural changes and increase in epithelial layer thickness on the OCT image. Further studies are required to assess tumour margins in vivo.

Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous fistula, compared to TEM alone and TEM following LCRT, which forced us to stop the study.

MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas

Oral squamous cell carcinoma (OSCC) and cutaneous squamous cell carcinoma (CSCC) are epithelial neoplasms, of which OSCC has a worse prognosis. Matrix metalloproteinases (MMPs) are involved in the initiation, invasion, metastasis, and defense of cancer. This study aimed to compare differences in MMP expression in these cancers. Sixty-one patients with early-stage (T1-T2 N0 M0) cancers, of which 36 were OSCC and 25 CSCC, were enrolled into this study. Immunohistochemical staining was performed with MMP-7, MMP-8, and MMP-9 antibodies. MMP-7 expression was stronger in OSCC than in CSCC, mainly in the invasive front. MMP-8 was absent and MMP-9 was mildly expressed in OSCC and CSCC cells. However, MMP-8 and MMP-9 were positive in peritumoral inflammatory cells in both cancers. In addition, MMP-7, MMP-8, and MMP-9 were not associated with the overall survival of patients with OSCC and CSCC patients. The increased expression of MMP-7 in the invasive front may partly explain the aggressiveness of OSCC.