Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma.

Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor-specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under-addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.

Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer.

BACKGROUND: Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor-positive early breast cancer receiving adjuvant endocrine therapy. METHODS: We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor-positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer-specific survival, distant recurrence as the first event, and overall survival were also assessed. RESULTS: A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer-specific survival also did not differ substantially between the two groups. CONCLUSIONS: Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor-positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.).

Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer.

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).

Current recommendations and recent progress in endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.

Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study.

BACKGROUND: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. METHODS: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). FINDINGS: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. INTERPRETATION: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. FUNDING: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial.

BACKGROUND: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. METHODS: In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m2, methotrexate 50 mg/m2, and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. FINDINGS: Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43). INTERPRETATION: Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy. FUNDING: Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).

Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.

Adjuvant and salvage radiotherapy after neoadjuvant therapy and radical prostatectomy for high-risk localized prostate cancer.

BACKGROUND: We sought to describe patterns of delivery of adjuvant (aRT) and salvage RT (sRT) in patients who underwent RP after receiving neoadjuvant androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC). METHODS: Two hundred eighteen patients treated on phase 2 neoadjuvant trials between 2006 and 2018 at two academic centers were evaluated. aRT and sRT were defined as receipt of RT with a PSA of ≤0.1 or >0.1 ng/mL, respectively. Primary outcomes were biochemical recurrence (BCR), defined as time from aRT/sRT to a PSA rising to >0.1 ng/mL, and metastasis-free survival (MFS) after RT. RESULTS: Twenty-three (11%) and 55 (25%) patients received aRT and sRT respectively. Median PSA at start of aRT and sRT was 0.01 and 0.16 ng/mL, and median duration from RP to RT was 5 and 14 months, respectively. All aRT patients had NCCN high-risk disease, 30% were pN1 and 43% had positive surgical margins; 52% had prostate bed RT. Fifty-one percent of sRT patients had biopsy Gleason 9-10, 29% were pT2 and 9% had positive surgical margins; 63% had RT to the prostate bed/pelvis. At a median follow-up of 5.3 and 3.0 years after aRT and sRT, 3-year freedom from BCR was 55% and 47%, and 3-year MFS was 56% and 53%, respectively. CONCLUSIONS: aRT was infrequently used in patients who received neoadjuvant ARPI before RP for HRLPC. Outcomes of aRT and sRT were similar but generally poor. Studies evaluating intensified systemic therapy approaches with postoperative RT in this high-risk population are needed.

A nationwide study of breast reconstruction after mastectomy in patients with breast cancer receiving postmastectomy radiotherapy: comparison of complications according to radiotherapy fractionation and reconstruction procedures.

BACKGROUND: We examined the patterns of breast reconstruction postmastectomy in breast cancer patients undergoing postmastectomy radiotherapy (PMRT) and compared complications based on radiotherapy fractionation and reconstruction procedures. METHODS: Using National Health Insurance Service (NHIS) data (2015-2020), we analysed 4669 breast cancer patients with PMRT and reconstruction. Using propensity matching, cohorts for hypofractionated fractionation (HF) and conventional fractionation (CF) were created, adjusting for relevant factors and identifying grade ≥3 complications. RESULT: Of 4,669 patients, 30.6% underwent HF and 69.4% CF. The use of HF has increased from 19.4% in 2015 to 41.0% in 2020. Immediate autologous (32.9%) and delayed two-stage implant reconstruction (33.9%) were common. Complication rates for immediate (N = 1286) and delayed two-stage (N = 784) reconstruction were similar between HF and CF groups (5.1% vs. 5.4%, P = 0.803, and 10.5% vs. 10.7%, P = 0.856, respectively) with median follow-ups of 2.5 and 2.6 years. HF showed no increased risk of complications across reconstruction methods. CONCLUSION: A nationwide cohort study revealed no significant difference in complication rates between the HF and CF groups, indicating HF for reconstructed breasts is comparable to CF. However, consultation regarding the fractionation for reconstructed breast cancer patients may still be necessary.

Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade.

BACKGROUND: The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS. PATIENTS AND METHODS: In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989-2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan-Meier analyses and Cox regression models were used. RESULTS: A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989-1998, 1999-2008 and 2009-2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC. CONCLUSION: Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.

Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Coping with modesty during radiotherapy for breast cancer: a multicentric study.

PURPOSE: Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. METHODS: The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. RESULTS: Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. CONCLUSION: This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

Outcomes from low-risk ductal carcinoma in situ: a systematic review and meta-analysis.

PURPOSE: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches. METHODS: PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast. RESULTS: Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk. CONCLUSION: This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials.

Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

Ethnic inequities in use of breast conserving surgery and radiation therapy in Aotearoa/New Zealand: which factors contribute?

PURPOSE: Aotearoa/New Zealand (NZ) faces ethnic inequities with respect to breast cancer survival and treatment. This study establishes if there are ethnic differences in (i) type of surgery and (ii) receipt of radiotherapy (RT) following breast conserving surgery (BCS), among women with early-stage breast cancer in NZ. METHODS: This analysis used Te Rehita Mata Utaetae (Breast Cancer Foundation National Register), a prospectively maintained database of breast cancers from 2000 to 2020. Logistic regression models evaluated ethnic differences in type of surgery (mastectomy or BCS) and receipt of RT with sequential adjustment for potential contributing factors. Subgroup analyses by treatment facility type were undertaken. RESULTS: Of the 16,228 women included, 74% were NZ European (NZE), 10.3% were Maori, 9.4% were Asian and 6.2% were Pacific. Over one-third of women with BCS-eligible tumours received mastectomy. Asian women were more likely to receive mastectomy than NZE (OR 1.62; 95% CI 1.39, 1.90) as were wahine Maori in the public system (OR 1.21; 95% CI 1.02, 1.44) but not in the private system (OR 0.78; 95% CI 0.51, 1.21). In women undergoing BCS, compared to NZE, Pacific women overall and wahine Maori in the private system were, respectively, 36 and 38% less likely to receive RT (respective OR 0.64; 95% CI 0.50, 0.83 and 0.62; 95% CI 0.39, 0.98). CONCLUSION: A significant proportion of women with early-stage breast cancer underwent mastectomy and significant ethnic inequities exist. Recently developed NZ Quality Performance Indicators strongly encourage breast conservation and should facilitate more standardized and equitable surgical management of early-stage breast cancer.

Surgically resectable nonsmall cell lung cancer: a contemporary approach.

New treatment paradigms for resectable nonsmall cell lung cancer (NSCLC), with an emphasis on personalised care and a multidisciplinary approach, have significantly improved patient outcomes. The incorporation of immune checkpoint inhibitors into neoadjuvant, perioperative and adjuvant treatment algorithms is reshaping the standard of care for resectable NSCLC. Adjuvant targeted therapy trials have also paved the way for a much-needed personalised approach for patients with actionable genomic alterations. Innovative surgical techniques and judicious use of postoperative radiotherapy may mitigate the toxicity associated with a multimodality approach. Amid the many new treatment options, questions remain about the best approach to consider for each patient. Measurement of minimal residual disease and achievement of pathological complete response are emerging biomarkers of interest to help further refine treatment selection. This review summarises the current management of resectable NSCLC, focusing on ongoing and recent advances in surgical approaches, the role of postoperative radiotherapy and the rapidly changing field of systemic therapies.

Is there role of adjuvant radiotherapy after complete resection of locally advanced nonsmall cell lung cancer?

PURPOSE OF REVIEW: This review aims to provide a timely and relevant overview of the role of postoperative radiotherapy (PORT) in completely resected stage IIIA-N2 nonsmall cell lung cancer (NSCLC). Given the controversy surrounding the use of PORT and the emergence of advanced radiation techniques and therapies, this review provides valuable insight into current and potential treatment strategies. RECENT FINDINGS: The Lung ART and PORT-C trials have provided valuable insights into the efficacy of PORT in stage IIIA-N2 NSCLC. While the results have been mixed, studies have shown that advanced radiation techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy, can reduce cardiopulmonary toxicities associated with PORT. Molecular targeted therapies and immunotherapies have also shown potential in improving NSCLC treatment outcomes. SUMMARY: The role of radiotherapy becomes smaller and smaller in new era. However, it is too early to abolish radiotherapy for all the patients after complete resection of locally advanced NSCLC. Nowadays, it is recommended to adopt individualized treatment approaches guided by multidisciplinary team consultations. The integration of IMRT, proton therapy, and emerging therapies offers the potential to enhance treatment efficacy while minimizing toxicity. Further research is needed to optimize the use of PORT and explore the method to identify the patients who can really benefit from PORT.

Nomogram-Based Risk Stratification to Identify Patients with T3N0M0 Breast Cancer with Survival Benefit from Postmastectomy Radiotherapy.

BACKGROUND: The survival benefit of postmastectomy radiotherapy (PMRT) for patients with T3N0M0 breast cancer remains controversial. This study aimed to identify patients with a survival benefit from PMRT by developing a novel risk stratification model. PATIENTS AND METHODS: The study recruited 2062 patients with pT3N0M0 breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database who underwent mastectomy between 2010 and 2019. Overall survival (OS) and breast-cancer-specific survival (BCSS) prognostic nomograms based on multivariate Cox regression were constructed to quantify the survival risk and classify patients into low- and high-risk groups. Subgroup analyses were undertaken to assess the role of PMRT according to age and risk stratification. RESULTS: In the overall cohort, PMRT was beneficial in improving OS in patients with pT3N0 breast cancer (5-year OS, non-PMRT versus PMRT: 76.6% vs. 84.2%, P < 0.001), while the benefit on BCSS was not significant (P = 0.084). On the basis of the risk stratification nomogram, in the high-risk group, PMRT improved OS in young patients by 10.1%, OS in elderly patients by 12.4%, and BCSS by 10.2% (P < 0.05), but the use of PMRT in the low-risk group did not improve OS and BCSS in all patients (P > 0.05). CONCLUSIONS: We presented a new method for quantifying risk using the nomogram to identify patients with high risk of pT3N0M0 breast cancer. This study found that older patients in the newly constructed high-risk group benefited from OS and BCSS benefits from PMRT, while for younger high-risk patients, there was only a benefit in terms of OS.

Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation.

BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy. PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence. RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR. CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

Surgical Perspectives on the Updated ASTRO Guideline on Partial Breast Irradiation for Breast Cancer.

This is an executive summary of the most recent American Society for Radiation Oncology (ASTRO) guidelines on use of partial breast irradiation in early-stage breast cancer.In the conscientious pursuit of "right-sizing" the management of patients with early-stage breast cancer, there has been an emphasis on judicious de-escalation of therapy. A component of this paradigm shift is partial breast irradiation (PBI), an approach characterized by targeted radiation therapy (RT) to lumpectomy cavity margins rather than to the whole breast (i.e., whole breast irradiation [WBI]) after breast conservation surgery (BCS). The American Society for Radiation Oncology (ASTRO) recently completed a revision of its evidence-based guidelines for the application of PBI.1To accomplish this, recent PBI data were reviewed by panel members, including representatives of the American Society for Radiation Oncology (ASTRO), in collaboration with the American Society of Clinical Oncology (ASCO), and the Society of Surgical Oncology (SSO), which provided representatives and peer reviewers. The guideline was approved by the ASTRO Board of Directors and endorsed by the Canadian Association of Radiation Oncology, European Society for Radiotherapy and Oncology, Royal Australian and New Zealand College of Radiologists, and the Society of Surgical Oncology.The recommendations focused on indications for PBI as an alternative to WBI and technical considerations specific to PBI. This editorial provides a summary and comments on the updated ASTRO PBI guidelines, offering insights into the implications of these findings for clinical practice and multidisciplinary decision-making while underscoring technical considerations for optimal incorporation of PBI into patient care.