Locoregional Disease Control Research Articles

Abstract OT1-21-01: Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET)

Abstract Background Five to eight percent of breast cancer (BC) patients present with distant metastasis at diagnosis, known as ‘de Novo’ metastatic breast cancer (dnMBC). Recent data showed that approximately 40% of dnMBC patients undergo locoregional treatment (LRT). LRT treatment modalities for metastasis and primary tumor benefit a subset of patients with oligometastatic disease. Our study group has recently demonstrated two prospective studies regarding this topic with favorable outcomes. MF07-01 IMET study, one of the first clinical randomized trials, showed that the patients with the diagnosis of dnMBC undergoing LRT followed by systemic therapy had an additional 14% OS benefit by the end of the 10-year follow-up when compared with others who received only systemic therapy. A prospective multicenter registry study MF14-01 BOMET also presented LRT prolonged survival and decreased locoregional recurrence in a prospective registry study with a median follow-up of 3 years. Timing of primary breast surgery either at diagnosis or after systemic treatment provided a survival benefit similar to systemic therapy alone in bone-only dnMBC patients. Although, the optimal timing of concurrent endocrine therapy, radiotherapy, and/or sequential surgery remains unclear. Hypothesis We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Objectives The primary objective is to perform a Phase I study to evaluate the feasibility of this curative intent treatment approach for patients with oligometastatic disease. Secondary objectives are to present the treatment response evaluating with CTC and/or ctDNA, and IHC and marker changes with multimodality treatments Methods Postmenopausal ER/PR (+) and Her2 neu (-), oligometastatic dnMBC patients will be enrolled in the study. Inclusion criteria: Primary breast tumor amenable for complete surgical resection, patients in good physical condition for receiving protocol-driven locoregional and systemic treatments and radiotherapy; Bone-only oligometastatic disease (5 or less metastasis); Primary tumor biopsy, metastatic site biopsy (ER/PR, Her2, Ki67). Exclusion criteria: Primary tumor not amenable for complete resection; primary tumor with extended infection, bleeding, or necrosis; patients with poor physical condition which prevents the patient from receiving protocol-driven locoregional and systemic treatment; synchronous primary cancer at the contralateral breast; clinically involved contralateral axillary nodes; patients not suitable for adequate follow-up, and failure to give informed consent. Study Design: • RT to the primary tumor (Hypo fractionated) + AI concurrent, Collect CTC and/or ctDNA • Add CDK4/6i to AI 2-4 weeks after RT + (6 months) • RT to bone metastasis (if still visible), Collect CTC and/or ctDNA + (12 months) • Primary Breast Surgery, Collect CTC and/orctDNA, ER/PR/Her 2 in the final specimen + • CDK4/6i +AI until progression and/or unmanageable toxicity Conclusion We hypothesize that in the era of modern radiotherapy and endocrine therapy, concurrent radiation and endocrine therapy will be non-inferior to sequential treatment modalities in terms of locoregional and systemic disease control in dnMBC. ER/PR (+), Her2 neu (-) oligometastatic dnMBC patients are potentially curable with multimodality treatments. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Kamuran İbis, Mutlu Dogan, M Selam, Kazim Senol, Secil Ak Aksoy, Mine Ozsen, Sibel Cetintas, Turkkan Evrensel, Efe Sezgin. Preoperative radiotherapy and systemic therapy following surgery in ‘de novo’ metastatic breast cancer (Protocol MF22-01; Intervention Systemic Treatment METastasis-ISTMET) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-21-01.

Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy

BackgroundIn patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that...

Hypofractionated Postmastectomy Radiotherapy (HF-PMRT): What did We Learn from COVID-19 Era?

Objectives: In breast cancer (BC) patients receiving mastectomy, postmastectomy radiotherapy (PMRT) improves long-term outcomes by decreasing local failure and cancer mortality. However, the optimal PMRT schedule is still under investigation. The present review aims to discuss the evidence regarding hypofractionated (HF) PMRT in BC patients in order to identify the optimal treatment approach. Additional purpose is to highlight what we have learned from COVID-19 era regarding HF schedules for PMRT in BC patients. Mechanism: Between February and November 2021, literature and database research were conducted. Key references were detected from a PubMed query. Range of publication date was between 2000 and 2021. Selection criteria included English language publications in humans. Hand searching included meeting proceedings of the European Society for Radiotherapy and Oncology (ESTRO), European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society for Radiation Oncology (ASTRO). The website clinicaltrials.gov was also searched. Randomized controlled trials evaluating HF-PMRT were included. Findings in brief: Our research returned 87 published papers. Fourteen trials were included in our final analysis. The comparisons of several different schedules of HF-PMRT with conventional fractionated PMRT provided similar results in terms of locoregional disease control without increasing toxicity. Particularly, an acute skin toxicity incidence grade 2 or higher ranged between 10 and 25% among the studies we analyzed. Conclusions: The present paper suggests that safety and efficacy of HF-PMRT is comparable with conventional schedules and standard practice guidelines are already available. COVID-19 pandemic has emphasised the need for increasingly tailored treatment protocols. Modern HF regimens should continue to be the standard of treatment in BC patients who receive PMRT also in the post-COVID-19 era.

Extension of lymph node dissection in the surgical treatment of esophageal and gastroesophageal junction cancer: seven questions and answers.

The role of two- or three-field nodal dissection in the surgical treatment of esophageal and gastroesophageal junction cancer in the minimally invasive era is still controversial. This review aims to clarify the extension of nodal dissection in esophageal and gastroesophageal junctional cancer. A basic evidence-based analysis was designed, and seven research questions were formulated and answered with a narrative review. Reports with little or no data, single cases, small series and review articles were not included. Three-field lymph node dissection improves staging accuracy, enhances locoregional disease control and might improve survival in the group of patients with cervical and upper mediastinal metastatic lymph nodal involvement from middle and proximal-third esophageal cancer.

Margin Free Resection Achieves Excellent Long Term Outcomes in Parathyroid Cancer.

Long-term outcomes of parathyroid cancer remain poorly documented and unsatisfactory. This cohort includes 25 consecutive parathyroid cancer patients with median follow-up of 10.7 years (range 4.1-26.5 years). Pre-operative work-up in the center identified a suspicion of parathyroid cancer in 17 patients. En bloc resection, including the recurrent laryngeal nerve in 4/17 (23.5%), achieved cancer-free resection margins (R0) in 82.4% and lasting loco-regional disease control in 94.1%. Including patients referred after initial surgery elsewhere, R0 resection was achieved in merely 17/25 (68.0%) of patients. Cancer-positive margins (R1) in 8 patients led to local recurrence in 50%. On multivariate analysis, only margin status prevailed as independent predictor of recurrence free survival (χ2 19.5, p < 0.001). Local excision alone carried a 3.5-fold higher risk of positive margins than en bloc resection (CI95: 1.1-11.3; p = 0.03), and a 6.4-fold higher risk of locoregional recurrence (CI95: 0.8-52.1; p = 0.08). R1-status was associated with an 18.0-fold higher risk of recurrence and redo surgery (CI95: 1.1-299.0; p = 0.04), and a 22.0-fold higher probability of radiation (CI95: 1.4-355.5; p = 0.03). In patients at risk, adjuvant radiation reduced the actuarial risk of locoregional recurrence (p = 0.05). When pre-operative scrutiny resulted in upfront oncological surgery achieving cancer free margins, it afforded 100% recurrence free survival at 5- and 10-year follow-up, whilst failure to achieve clear margins caused significant burden by outpatient admissions (176 vs. 4 days; χ2 980, p < 0.001) and exposure to causes for concern (1369 vs. 0 days; χ2 11.3, p = 0.003). Although limited by cohort size, our study emphasizes the paradigm of getting it right the first time as key to improve survivorship in a cancer with excellent long-term prognosis.

Concomitant Use of Biopsy Clips and Wire Localization in Invasive Breast Cancer is Associated With Successful Clip Retrieval

IntroductionSurgical management of the axilla in patients with clinically node-positive breast cancer has shifted to less invasive surgical approaches, such as sentinel lymph node dissection (SLND) and targeted axillary dissection (TAD). Successful retrieval of the biopsy clip marking the lymph node of interest is crucial for assessment of pathologic response and locoregional disease control. MethodsWe performed a retrospective review of patients ≥18 years old with invasive breast cancer and biopsy-proven axillary LN involvement, who underwent LN clip placement from January 2012 to July 2017 at Johns Hopkins Hospital. ResultsOf the 128 eligible patients, the median age at diagnosis was 51.5 years (range, 23-92 years) with predominately stage T2-3 disease (54.7% T2, 42.2% T3), of ductal histology (76.6%), and located in the upper outer quadrant (42.2%). Among the 63.3% (81) of patients who received neoadjuvant systemic therapy, 43.2% (35) had a partial response and 30.9% (25) had a complete response. Axillary procedures performed consisted of 36.7% (47) SLND/TAD, 53.9% (69) ALND, and 9.4% (12) SLND/TAD with conversion to ALND. The clipped LN was successfully retrieved in 63.8% (30) of SLND/TADs, 39.1% (27) of ALNDs, and 58.3% (7) of SLND/TADs followed by ALND. Pre-operative node localization by wire and/or skin markings was performed for 16.4% (21) of patients. Among these, 90.5% (19) of clipped LNs were successfully retrieved, compared to 42.1% (45) retrieved in axillary procedures without preoperative node localization. ConclusionUse of preoperative targeted node localization improved rate of clipped LN retrieval across all three types of axillary procedures.

Reirradiation with Photon Radiotherapy for Recurrent or New Primary Breast Cancer after Prior Breast Irradiation

<h3>Purpose/Objective(s)</h3> Recurrent or new primary breast cancer may benefit from the local and/or regional recurrence risk reduction provided by RT, but delivery of a repeat course of RT is challenging due to risks of potential serious toxicities to organs at risk. This has led to limited use and heterogeneous practice patterns of salvage RT delivery. We hypothesize that breast cancer reirradiation (reRT) may be feasible using modern photon treatment techniques, and we present clinical outcomes and toxicities from a large single institution cohort. <h3>Materials/Methods</h3> In an IRB-approved retrospective study, all consecutive patients with recurrent or new primary non-metastatic breast cancer treated with breast or chest wall (CW) RT and photon reRT from a single institution were identified. Patient and tumor characteristics, treatment parameters, clinical outcomes and toxicities were collected. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) were defined from reRT start to date of any recurrence, distant recurrence, and death or last follow-up and estimated using Kaplan-Meier methodology. <h3>Results</h3> In total, 126 consecutive patients treated with reRT from 2013-2020 met criteria for analysis. Median age at reRT was 65 years (range 39-88). ReRT was delivered with 3DCRT in 47.6%, VMAT in 46.0%, and static IMRT in 6.4%. Median first, second, and cumulative prescription doses were 60.0 Gy, 46.4 Gy, and 105.0 Gy, respectively. Most received whole breast (WB) (80.2%) or partial breast (PB) (8.7%) initial RT. At reRT, 30.9% were treated to the PB, 11.1% WB/CW, 37.3% WB/CW with comprehensive regional lymph nodes (LN), and 12.8% WB/CW with partial regional LN. Median time between RT courses was 95 months (range 10-361). At a median follow-up of 26.5 months, 9 patients had died. Locoregional, distant, and any recurrence developed in 15 (11.9%), 22 (17.5%), and 28 (22.2%) patients, respectively. Estimated 3-year RFS was 80.7%, DMFS was 80.9%, and OS was 93.2%. Eleven (8.7%) patients developed grade 3 (G3) toxicities (dermatitis (n=8), acute (n=1) and late (n=1) CW pain, decreased joint range of motion (ROM) (n=1)); no G4 or G5 toxicities occurred. Five (4.0%) patients developed rib fracture. Of 23 patients retreated to a reconstructed CW, 30.4% and 34.8% developed Baker G1-2 or G3-4 implant contracture, respectively. Four patients had significant brachial plexus overlap, of whom 1 developed G2 decreased joint ROM and G2 soft tissue fibrosis and 1 developed G3 decreased joint ROM. <h3>Conclusion</h3> In the largest institutional experience to date on the use of photon reRT for recurrent or new primary breast cancer, reRT is associated with low rates of severe adverse events. In this high-risk population, locoregional and distant disease control rates are high. Further prospective study is needed to define the optimal treatment volume, prescription dose selection, and cumulative dose constraints with reRT to maximize the likelihood for successful and safe salvage therapy.

Acute and Long-Term Toxicity of Whole Pelvis Proton Radiation Therapy for Definitive or Adjuvant Management of Gynecologic Cancers

<h3>Purpose/Objective(s)</h3> The purpose of this study is to characterize long term toxicity and clinical outcomes of patients treated with whole pelvis (WP) pencil beam scanning proton therapy (PBSPT) for gynecologic malignancies. <h3>Materials/Methods</h3> We retrospectively reviewed the records of 23 patients treated from 2013 to 2019 with WP PBSPT for endometrial, cervical and primary vaginal cancer at our institution. We report acute and late Grade (G) 2 or higher toxicities, graded by physicians and nurses according to the Common Terminology Criteria for Adverse Events, Version 5. The late period was defined as greater than 6 months from end of RT. Disease outcomes, including freedom from (FF) local recurrence, FF regional recurrence, FF distant recurrence, and FF any recurrence were assessed using the Kaplan-Meier method. <h3>Results</h3> Median age was 59 years. 12 (52%) of patients had uterine cancer, 10 (43%) had cervical, 1 (4%) had vaginal. 22 (96%) had intermediate-high risk disease. 20 (87%) were treated post operatively. 3 (13%) received definitive chemoRT. The median PBSPT dose was 50.4 Gy (range, 45-62.5). 10 (43%) received an additional brachytherapy boost. 22 patients (96%) received chemotherapy, 12 of those concurrently with RT. Median follow up was 57.7 months. 5-year actuarial FF local recurrence was 95.5%, FF regional recurrence was 90.9%, FF distant recurrence was 74.7%, and FF any recurrence was 71.2%. There were 2 deaths related to cancer progression. In the acute period, 2 patients (8.6%) had G2 genitourinary (GU) toxicity. 5 had G2 and 1 had G3 gastrointestinal (GI) toxicity, for a total of 6 patients (26%) with G2-3 GI toxicity. 17 (74%) had G2-4 hematologic (H) toxicity. In the late period, 3 patients (13%) had G2 GU toxicity, 1 (4%) had G2 GI toxicity, and 2 (8.6%) had G2-3 H toxicity. <h3>Conclusion</h3> WP PBSPT for gynecologic malignancies delivers favorable locoregional disease control with the majority of recurrences occurring at distant sites. Rates of GU and GI acute and late toxicity are low. Acute hematologic toxicity was most common, likely related to chemotherapy.

CAN THE TUMOR SITE AFFECT THE PROGNOSIS OF SALIVARY GLAND CANCER? A SYSTEMATIC REVIEW AND META-ANALYSIS

<h3>Objectives</h3> To assess the association between primary sites of salivary gland tumors (SGTs) and prognosis. <h3>Study Design</h3> Studies from 5 databases were assessed and a meta-analysis was performed using studies that presented 95% CI, hazard ratio (HR), and survival analysis. QUIPS (Quality in Prognosis Studies) was used to assess the methodological quality of included studies, and GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence. <h3>Results</h3> Results from 46,361 patients showed that site had a prognostic effect on SGTs. Tumors involving minor salivary glands showed worse overall survival (HR = 1.60; 95% CI, 1.17-2.19; <i>P</i> = .003), disease-specific survival (HR = 1.63; 95% CI, 1.12-2.37; <i>P</i> = .01), and cause-specific survival (HR = 2.10; 95% CI, 1.72-2.55; <i>P</i> = .00001). Tumors from major salivary glands showed better recurrence-free survival (HR = 2.31; 95% CI, 1.77-3.02; <i>P</i> = .00001) and locoregional control of disease (HR = 2.66; 95% CI, 1.20-5.91; <i>P</i> = .02). <h3>Conclusions</h3> Our results showed that the primary site of SGTs has an effect on survival and patient prognosis.

Assessing long-term locoregional control of spinal osseous metastases after microwave ablation

Osseous metastases to the spine result in significant pain and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of microwave ablation (MWA) for the treatment of spinal metastases regarding pain reduction and local control of disease progression. In this single center retrospective study, patients with osseous metastases to the spine undergoing MWA with vertebroplasty from 2013 to 2020 were included. Locoregional control of metabolic activity at the treated level was assessed using PET/CT scan both pre- and post-procedure. Pain reduction was measured using change in visual analog scale (VAS) pain score. Forty-eight spinal levels were treated with MWA in 28 patients (57 % male, mean age 68 ± 9 years). Median ablation time, energy, and temperature were 4 min and 13 s, 3.6 kJ, and 80 °C, respectively. Median pre-procedure maximum standard uptake value (SUVmax) was significantly reduced following ablation, from 4.55 (IQR 3.65–6.1) to 0 (IQR 0–1.8; p < 0.001), over an average of 29 ± 14.1 month follow up period. Pre-procedure VAS pain score was reduced from median (IQR) of 8 (6.5–9) to 1(1–2), 2(1–3) and 1(0.5–3) at 24 h, four weeks, and six months post-procedure, respectively (all p < 0.001 with respect to pre-procedure scores). In conclusion, this study supports microwave ablation as an effective technique for pain palliation and long-term locoregional tumor control of oligometastatic spinal disease as assessed by metabolic response.

Abstract No. 563 Yttrium-90 radiation segmentectomy for neuroendocrine tumor liver metastases

Yttrium-90 (Y-90) radioembolization is a liver-directed treatment option for patients with neuroendocrine tumor liver metastases (NELMs), but there are concerns of long-term hepatotoxicity. Radiation segmentectomy (RS) has been described in hepatocellular carcinoma, selectively delivering tumor-ablative radiation doses in a parenchymal-sparing approach. We hypothesize that RS of NELMs can achieve considerable locoregional disease control with a positive safety profile.

Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis.

Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV-counterparts, thereby pushing the adoption of de-intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de-intensification in terms of overall survival (OS), progression-free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n=48 studies with data available, de-intensified treatments reduced OS in HPV+ OPCs (HR=1.33, 95% CI 1.17-1.52; p < 0.01). In de-escalated treatments, PFS was also decreased (HR=2.11, 95% CI 1.65-2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR=2.51, 95% CI 1.75-3.59; p < 0.01; and HR=1.9, 95% CI 1.25-2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR=1.42, 95% CI 1.16-1.75; p < 0.01). When adjuvant treatments were compared, standard and de-escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de-escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub-optimal treatment to patients.

Clinical results of PERICLES: A phase II trial investigating atezolizumab +/- radiotherapy for advanced squamous cell carcinoma of the penis.

3 Background: Patients (Pts) with advanced squamous cell carcinoma of the penis (aPeCa) have a poor prognosis (21% 2-year overall survival from moment of diagnosis) and high morbidity, due to progressive locoregional disease. Pre-clinical studies show high rates of infiltrating immune cells and high PD-L1 expression, suggesting that immunotherapy may be beneficial for these patients. In the PERICLES study, we assess the activity of atezolizumab (atezo) in aPeCa pts, with or without radiotherapy (RT) to control locoregional lymph node disease. Methods: A single-centre phase 2 study with two treatment arms (non-randomized) was conducted in 32 histologically confirmed aPeCa pts with a WHO performance status of 0-1 (NCT03686332). Any previous treatment except for immunotherapy was allowed. Study treatment consisted of atezo 1200 mg every 3 weeks (all pts). Pts expected to benefit from RT for locoregional disease control (cohort A) additionally received 33 fractions of 1.5 Gy (locoregional affected lymph node regions and penile region) and 1.8 Gy (macroscopic tumor + margin) irradiation. Response was evaluated with 12-weekly CT scans of the abdomen and thorax using RECIST1.1. Toxicity was scored by NCI-CTCAE V4. The primary endpoint was 1-year progression free survival (PFS) for the full cohort. Results: From Oct 2018 to Aug 2021, 20 pts were included in cohort A (RT + atezo) and 12 pts in cohort B (only atezo). Median follow-up was 22 months (interquartile range (IQR) 4.3-14). Median age was 67 years (IQR 60-72) and all patients had stage IV aPeCa. Pts received no prior treatment (25%), or prior RT (34%), chemoradiation (22%), chemotherapy (6%) or surgery (69%). An immunotherapy or radiotherapy-related grade 3-4 AE was observed in 3/32 (9.4%) and 1/20 (5.0%) patients, respectively. There were no grade 5 treatment-related AEs. One-year PFS was 12% (95% confidence interval (CI) 4.0-33), which did not meet the primary objective. The response rate of RECIST1.1 evaluable pts was 30% (see table). In two patients with pulmonary metastases, a complete response was observed. Initial responses with early progression were seen in 5 pts. Median overall survival (OS) was 12 months (95% CI 5.4-19). Conclusions: Anti-tumor activity of atezo was observed in aPeCa, including complete and durable responses. The trial failed to meet its primary objective (PFS). Our results suggest that a subset of aPeCa pts has incomplete immunological activity and/or early resistance to atezo. Analysis of tumor tissue collected in this trial (including on-treatment biopsies) could suggest new therapeutic strategies to overcome resistance and improve clinical outcome to immunotherapy in aPeCa. Clinical trial information: NCT03686332. [Table: see text]

Abstract ES9-1: Local therapy of the primary tumor in de novo Stage IV breast cancer

Abstract Background: Distant metastases are present in 6% or more of newly diagnosed breast cancer patients, worldwide. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival and local control, based on multiple retrospective studies, but clinical trials have reported conflicting results. Methods: All four completed trials included women presenting with metastatic breast cancer and an intact primary tumor. The trial design mandated initial systemic therapy prior to randomization in two trials (EA2108 and Tata Memorial) with subsequent randomization to locoregional therapy (LRT) or not, if there was no progression. In two other trials (MF 07-01 and POSYTIVE) randomization occurred upfront. LRT consisted of surgery and radiotherapy per standards applied to patients with non-metastatic disease, with minor differences between trials. The primary endpoint was two or three year overall survival in all four trials, with locoregional control and quality of life as secondary endpoints. Progression-free survival was also examined. The randomized sample size ranged from 93 to 350 across the trials (the POSYTIVE trial did not reach full accrual). Tumor characteristics were balanced between arms, except MF 07-01, which favored the LRT arm. Prospectively measured quality of life (QoL) outcomes have been reported for POSYTIVE and EA2108, assessed using standard instruments. Results. The design, accrual, and main results of the four completed trials, and one still in follow-up (Shien, JCOG 1017) are shown in the Table. Median follow-up duration at the time of reporting ranges from 23 to 53 months in these trials. The overall survival in three of four trials shows no advantage with the use of LRT. MF 07-01 is an outlier, with improved 5-year OS in the LRT arm. Of note, survival rates vary across the trials, depending on the resource environment; in the Tata (India) trial this was 20 months at 2 years, and in EA2108 (USA and Canada) it was 53.1 months (95% CI: 47.9,-) in the systemic therapy arm and 54.9 months (95% CI: 46.7,-) in the locoregional therapy arm. Locoregional progression rates were significantly lower in those randomized to primary site LRT, with locoregional progression occurring in less than 20% of patients treated with LRT with systemic therapy. However, in the systemic therapy alone arms, a minority of patients (under 20%) required palliative LRT, demonstrating the efficacy of contemporary systemic therapy in avoiding symptomatic locoregional progression. Despite the improved local control however, quality of life measures were largely similar between arms in the two trials where prospective, preplanned evaluation of these parameters has been reported (POSYTIVE and EA2108). Conclusions: The preponderance of current evidence does not support use of early locoregional therapy for the primary site as a means to improve survival in patients presenting with metastatic breast cancer. However, LRT was associated with improved locoregional disease control, albeit with no overall impact on quality of life. Questions remain regarding the survival value of primary site LRT in the oligometastatic setting, since this aspect has not been prospectively examined in any existing trial. Phase III trials testing primary site local therapy in de novo Stage IV breast cancersystemic therapy firstAccrual period.Randomized NOverall survival HR (95% CI)Locoregional progression-free survivalBadwe (India)Yes2005-123501.04 (0.84, 1.34)0.16 (0.10, 0.26)Khan (USA &amp; Canada)Yes2011-152561.11 (0.82, 1.52)0.35 (0.21, 0.57)Shien (JapanYes2011-16407Not reportedNot reportedSoran (Turkey)No2008-122740.66 (0.49, 0.88)1% vs. 11%Fitzal (Austria)No2010-19930.69 (0.36, 1.33)8.9% vs. 17.8% Citation Format: S Khan. Local therapy of the primary tumor in de novo Stage IV breast cancer. [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES9-1.

External Radiotherapy for Locoregional Control in Thyroid Carcinoma.

Most patients with well-differentiated thyroid cancers (WDTC) are adequately treated with surgery, radioactive iodine, and TSH suppressionby thyroxine. External radiotherapy (ERT) is reserved for selected cases and for older patients. Some of the indications for ERT to neck include adjuvant treatment for gross or microscopic disease after surgery, palliation of locally advanced unresectable tumor, or as salvage for recurrent disease which is not amenable to surgery or does not uptake radioactive iodine. High radiation dose of at least 60Gy is required for locoregional control of gross or microscopic residual disease. As even patients with recurrent or metastatic disease can have long survival, it is important to minimize late radiation-induced morbidity without compromising local control. Modern ERT technique like intensity-modulated radiotherapy allows high radiation dose to be delivered to the large, complex target volume while protecting the adjacent critical normal structures like the trachea, larynx, esophagus, and cervical spinal cord.

Impact of Tumor Dosimetry on Clinical Outcomes after Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma

We hypothesized that escalated biological effective dose (BED) via stereotactic body radiation therapy (SBRT) would improve outcomes for patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC).A retrospective review was performed on consecutive patients who received pancreas SBRT from June 2009 to June 2020, were non-metastatic at the time of SBRT, received neoadjuvant chemotherapy, and had available gross tumor volume (GTV) dosimetry. Variables of interest included: age, gender, tumor location (body/tail vs head/neck), chemotherapy type (5-fluorouracil-based vs gemcitabine-based), AJCC V8 stage, pre- and post-radiotherapy (RT) CA19-9, GTV D95, and GTV V55-40 Gy. GTV volume variables were analyzed as continuous (cont) and as binary (+) functions. All patients with BRPC at diagnosis were analyzed by a logistic regression model for variables that predicted a higher likelihood of undergoing surgical resection (Model A). A second model of all patients (BRPC and LAPC) unable to undergo surgery was constructed by Cox regression analysis investigating variables that predicted for improved overall survival (OS), progression free survival (PFS), time to loco-regional failure (TTLRF), and time to distant failure (TTDF; Model B). All clinical time points were calculated from the end of SBRT and data analysis was performed in SAS with backward elimination variable selection.A total of 365 patients had a median follow up from SBRT of 12.1 months and 251 patients (69%) were diagnosed with BRPC. Model A composed of 200 BRPC patients (56% resected) with 3 clinical variables: chemotherapy (P = .39), AJCC stage (OR 0.54, P = 0.01), post-RT CA19-9 (OR 0.27, P = < 0.001); and 3 dosimetric variables: GTV D95 (OR 3.81, P = 0.03), GTV V40+ (OR 2.52, P = 0.07), and GTV V40cont (OR 0.98, P = 0.03). Model B included 168 patients (51% BRPC) unable to undergo surgery. In this group, 5-fluorouracil-based chemotherapy was associated with improved OS (HR 0.51, P = < 0.001), PFS (HR 0.48, P = < 0.001), TTLRF (HR 0.47, P = 0.004), and TTDF (HR 0.54, P = 0.006). GTV V40+ was significantly associated with improved PFS (HR 0.59, P = 0.005) and TTLRF (HR 0.58, P = 0.036), but not with OS (HR 1.06, P = 0.78) or TTDF (HR 0.68, P = 0.113). Pre-RT CA19-9 was associated with worse OS (HR 1.43, P = 0.010) and TTLRF (HR 1.59, P = 0.022). The proportion of patients receiving 5-flurouracil-based chemo and achieving GTV V40+ was evenly distributed across the cohort (χ2 = 0.55, P = 0.45).In the largest series of pancreatic cancer SBRT to date, dose-escalated tumor coverage specifically to 40 Gy (BED10 = 72 Gy) increases the likelihood of surgical resection in patients with upfront BRPC and is associated with improved PFS that is driven by improvement in loco-regional disease control for unresected patients. These data may help to inform the evolving landscape on the use of neoadjuvant and definitive radiotherapy in pancreatic cancer.

Narrative review of the role of yttrium-90 selective internal radiation therapy in the surgical management of colorectal liver metastases.

The management of colorectal liver metastasis (CRLM) is complicated and benefits from a multidisciplinary team approach. Liver-directed therapy has been emerging as a modality for better progression-free control. In its early years, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) was confined as an end-of-line therapy. However, literature has supported other roles including: a first-line treatment for CRLM alone or in combination with systemic chemotherapy; an adjunct to second or third-line chemotherapy; and a salvage treatment for chemo-refractory disease. Although future liver remnant (FLR) hypertrophy may take 3-12 months, the SIRT effect on loco-regional disease control has rendered it to be a useful tool in some pathologies with certain strategic goals. This paper reviews the use of SIRT with Y-90 in a surgical treatment pathway. This includes: (I) an element of multidisciplinary treatment of low-volume CRLMs, (II) convert an R1 to R0 resection by sterilizing the margins of tumor near critical structures, and (III) radiation lobectomy to induce contralateral hypertrophy in order to aid in a safer resection. There are many opportunities to validate the role of SIRT as a first-line therapy along with surgical resection including an umbrella clinical trial design.

Metastatic disease to the liver: Locoregional therapy strategies and outcomes

Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.

Locally advanced anorectal malignant melanoma in septuagenarian patient treated by laparoscopic abdominoperineal resection: A case report.

IntroductionAnorectal malignant melanoma (ARMM) is a rare disease with a poor prognosis. In cases involving locally advanced disease, the treatment strategy is difficult, especially in octogenarian patients, because the prognosis is poor, despite the corresponding decrease or loss of the anal function.Presentation of caseA 78-year-old woman was admitted to a local hospital with chief complaints of severe anal discomfort due to an egg-sized tumor that was protruding out of the anus and melena. A diagnosis of ARMM was confirmed based on the examination of biopsy specimens and imaging study showed swollen lymph nodes on the dorsal side of the middle rectum and left internal iliac lymph nodes.Laparoscopic abdominoperineal resection with left lateral lymph node dissection was performed. The examination of the resected specimen revealed two polypoid tumors with a maximum diameter of 38 mm and 14 mm with a metastatic lymph node of 62 mm in the mesorectum. The postoperative course was uneventful. Relapse and local recurrence free survival without any complaints was obtained for more than 12 months.DiscussionWith respect to locoregional disease control, it has been reported that abdominoperineal resection can obtain better control of local disease in comparison to local resection. Laparoscopic surgery is advantageous in its facilitation of an early postoperative recovery for elderly patient.ConclusionLaparoscopic abdominoperineal resection may control locoregional disease and improve the patient's QOL with early postoperative recovery. —even in septuagenarian patients—may become a treatment strategy for advanced ARMM.

Survival Outcomes of Salvage Metastasectomy After Failure of Modern-Era Systemic Therapy for Melanoma.

Metastasectomy for selected patients with melanoma was associated with improved survival in the era before effective systemic therapy. Emerging evidence shows that these benefits persist even in this era of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. This study aimed to evaluate the outcomes of salvage metastasectomy after failure of systemic therapy. Stage 3 or 4 melanoma patients with extracranial disease progression after at least 4 weeks of systemic treatment between 2009 and 2020 were identified and categorized as resected to no evidence of disease (NED), non-progressive residual disease (NPRD), or progressive residual disease (PRD). Systemic therapy was stratified into BRAF-targeted therapy, immune checkpoint inhibitor immunotherapy, or both. The end points of overall survival (OS), progression-free survival (PFS), and locoregional disease control (LRC) were assessed using Kaplan-Meier curves. Uni- and multivariable Cox regression procedures were used to examine factors associated with OS, PFS and LRC. The study enrolled 190 patients. Among all the patients, the 5-year OS from metastatectomy was 52%, the 3-year PFS was 21%, and the 5-year LRC was 61%. After resection to NED, NPRD, and PRD, the 5-year OS values were 69%, 62% and 8%, respectively. Fewer lines of preoperative therapy, use of preoperative immunotherapy, and resection to NED were predictors of improved OS. After resection to NED, NPRD, and PRD, the 3-year PFS values were 23%, 24% and 10%, and the 5-year LRC values were 61%, 72% and 34%, respectively. Salvage metastasectomy was associated with durable survival and disease control, particularly after resection to NED, preoperative immunotherapy, and fewer lines of preoperative systemic therapy.