Study protocol for JCOG1807C (DEEP OCEAN): a interventional prospective trial to evaluate the efficacy and safety of durvalumab before and after operation or durvalumab as maintenance therapy after chemoradiotherapy against superior sulcus non-small cell lung cancer.

BACKGROUND: Superior sulcus tumours (SSTs) are relatively uncommon and one of the most intractable lung cancers among non-small cell lung cancer (NSCLC). We planned a multicenter, single-arm confirmatory trial of new multidisciplinary treatment using immune-checkpoint inhibitor. The aim is to evaluate the safety and efficacy of new multidisciplinary treatment with perioperative durvalumab after chemoradiotherapy (CRT). METHODS: The primary endpoint is 3-year overall survival. Patients receive induction CRT with sequential two courses of durvalumab, followed by surgical resection for resectable SST. The regimen for CRT is two courses of cisplatin and S-1, and concurrent radiotherapy (66 Gy/33 Fr). After surgery, 22 courses of post-operative durvalumab therapy are administered. For unresectable SST, an additional 22 courses of durvalumab are administered after induction durvalumab. RESULTS: In two cases as a safety cohort, the safety of intervention treatment up to 30 days after surgery was examined, and there were no special safety signals. Patient enrollment has now resumed in the main cohort. CONCLUSIONS: The results of this study may contribute to the establishment of a new standard of care for SST, which is an intractable NSCLC.

Neoadjuvant nivolumab plus chemotherapy followed by resection for superior sulcus tumour with high PD-L1 expression: A case report.

The standard treatment for resectable non-small cell lung cancer (NSCLC) located in the superior sulcus is neoadjuvant chemoradiotherapy followed by highly invasive resection. Based on the results of the CheckMate 816 trial, which showed a marked improvement in the efficacy of neoadjuvant chemo-immunotherapy, we report a case of minimally invasive resection after neoadjuvant nivolumab plus chemotherapy for superior sulcus NSCLC, resulting in a pathologic complete response. The patient was a 76-year-old man with a 65-mm right superior sulcus tumour diagnosed as squamous cell carcinoma with 95% PD-L1. After two courses of neoadjuvant nivolumab plus chemotherapy, the tumour was completely resected through an 11-cm right lateral thoracotomy with second rib resection and first rib preservation. No residual tumour cells were observed in the specimen, and the patient had a pathologic complete response. This report represents a new treatment option for superior sulcus tumours.

Surgical management of superior sulcus tumors: A twenty-year experience of an oncological high volume referral centre.

Objectives: Superior sulcus tumour, which affects the lung's apex, is an uncommon subtype of non-small cell lung cancer (NSCLC). The current study examined the clinical characteristics and management of superior sulcus NSCLC patients in a high-volume referral oncological centre over 22 years. Methods: Retrospective review of 100 surgeries with curative intent for superior sulcus NSCLC over 22 years (July 1998 - December 2020). The surgical approach was defined according to the lesion site and the anatomy of the thoracic inlet. Survival curves, including non-cancer-related deaths, were drawn using the Kaplan-Meier methods, and the log-rank test was used to evaluate differences in survival across groups of patients. Cox proportional hazards regression was used to assess the association between selected clinical and pathologic characteristics on OS. Results: 54 patients received induction treatments. The surgical approach was anterior thoracotomy in 53 patients, Paulson incision in 30, and a combined in 8. The median postoperative length of stay was 11 days (range: 5 - 27 days). Overall 90-day mortality was 6.93%. The median OS was 24.3 months. After a median follow-up of 3 years, 5-year and 10-year OS rates were 33.9% and 26.4%, respectively. A significantly lower 5-year OS was observed in patients with the nodal disease (46.6% in pN0 vs 13.2% in pN+; p = 0.024), without preoperative treatments (41.0% in patients without preoperative treatments versus 17.4%; p = 0.09) and anteriorly located tumour (anterior vs posterior: 17.4% vs 49.1%; p = 0.032). Cox proportional hazards regression showed better survival in the pT1 stage (HR = 4.6; 95% CI: 1.9 - 11.2; p = 0.00076) and in R0 (HR = 4.2; 95% CI: 1.4 - 12.5; p = 0.010). Conclusions: Superior sulcus tumours still represent a life-threatening condition that, while curable in a significant proportion of cases, requires complex procedures with high surgical risks and a multimodality treatment setting. An optimal surgical approach should be planned to maximise resection completeness and survival. Other factors affecting survival are related to tumour staging, emphasising the importance of a meticulous preoperative workup and candidate selection to identify those expected to benefit from a survival benefit.

A Nearly Missed Pancoast Tumour From Isolated Persistent Leg Pain.

Pancoast tumours (PTs) are apical tumours of the lung that manifest with a variety of symptoms. Herein, we describe a rare case of a 56-year-old female with a one-month history of persistent left leg pain despite advanced imaging, such as magnetic resonance imaging (MRI), and orthopaedic input, which was focused onto her left knee being the prime cause of her pain. Her non-resolving symptoms prompted her to attend the Emergency Department. A careful clinical examination pointed towards the left proximal tibia being the most probable cause. Basic radiographic imaging (x-ray) of the left tibia revealed a lytic lesion which was later confirmed to be metastatic disease arising from a Pancoast tumour (PT) following further advanced imaging and diagnostics. This case highlights a unique presentation of a Pancoast tumour that, to our knowledge, has never been reported before in the medical literature. A high index of suspicion, careful examination, and investigation were essential to reach this diagnosis.

Trimodality therapy for superior sulcus tumour: experience of a single institution over 19 years.

OBJECTIVES: Induction chemoradiotherapy followed by surgery is the standard treatment for superior sulcus tumours (SSTs). However, the protocols, chemotherapy agents and cycles used as well as the mode and intensity of radiotherapy vary between institutions. Thus, the objective of the study was to investigate the effects of trimodality therapy on the outcomes of patients with SSTs. METHODS: Sixty patients with SSTs were enrolled between January 1999 and December 2017. Induction therapy consisted primarily of 2 cycles of mitomycin-vindesine-cisplatin or cisplatin-vinorelbine delivered concurrently to the tumour with 40-45 Gy of radiation. Surgery was performed 2-6 weeks after completion of induction therapy. RESULTS: Fifty-four (90%) patients underwent radical surgical resection. Complete pathological resection was achieved in 44 patients (81%). There was no 30-day mortality. After a median follow-up of 57.0 months, 19 (35%) patients experienced recurrence, and 8 (15%) patients showed brain metastasis. A pathological complete response (PCR) was observed in 12 (22%) patients. The 5-year survival rate for the entire population (n = 54) was 69% (95% confidence interval 55-81%). The survival rate was better for patients who underwent complete resection than for those who underwent incomplete resection (73% vs 51%, P = 0.46). A better survival rate was evident in patients with PCR than in those without PCR (92% vs 62%, P = 0.12). CONCLUSIONS: Trimodality therapy for SSTs was efficacious and associated with favourable outcomes, with acceptable morbidity and mortality. PCR in patients with resected SSTs reveals promising long-term survival prospects with the trimodality therapy.

Does induction chemoradiotherapy increase survival in patients with Pancoast tumour?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether induction (neoadjuvant) chemoradiotherapy (iCRT) compared with other therapeutic strategies improves survival in patients with Pancoast tumours. Altogether 248 papers were identified using the below-mentioned search. Ten of them represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. Four studies were retrospective comparative studies of induction chemoradiotherapy and surgery (trimodal therapy) versus other therapeutic strategies. Two studies were retrospective and four were prospective investigating trimodal therapy. These papers comprised a total of 550 patients. The overall survival was better with trimodal therapy compared with RT (radiotherapy) followed by surgery group in all three comparative studies. The 2-year survival varied in the trimodal therapy group from 70 to 93%, in comparison to RT group where variation was from 22 to 49%. Five-year survival for trimodal therapy varied between 36.4 and 84% in the results of two comparative studies, compared with 11 and 49% for RT and surgery, respectively. One paper looked at survival in patients who underwent surgery alone [30% at 2-year and 20% at 4-year overall survival (OS)]. The 5-year OS in the retrospective group varied between 38 and 59%. Similar results were reported for the prospective group with 5-year OS between 44 and 56%. Despite a large variation in pCR (complete pathological response) (15-93%) and R0 (77-100%) reported, both represented a positive prognostic factor for survival. Three papers looked at the impact of staging following induction chemoradiotherapy. The majority of patients had T3 disease. An advantage in survival was seen in patients with early disease compared with advanced stage. No randomized controlled trials were identified. All the 10 articles suggested there was a benefit in trimodal therapy with improvement in overall survival. We conclude that combining induction chemoradiotherapy with surgery for Pancoast tumour may offer a survival benefit compared with radiotherapy with surgery or surgery alone.

Results of surgical resection after induction chemoradiation for Pancoast tumours †.

OBJECTIVES: Pancoast tumour is a rare neoplasia in which the optimal therapeutic management is still controversial. The traditional treatment of Pancoast tumour (surgery, radiotherapy or a combination of both) have led to an unsatisfactory outcome due to the high rate of incomplete resection and the lack of local and systemic control. The aim of the study was to determine the efficacy of the trimodality approach. METHODS: Fifty-six patients (male/female ratio: 47/9, median age: 64 years) in stage IIB to IIIB were treated during a period between 1994 and 2013. Induction therapy consisted of 2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30-44 Gy). After restaging, eligible patients underwent surgery 2 to 4-week post-radiation. RESULTS: Thirty-two (57.1%) patients were cT3 and 24 (42.9%) cT4, 47 (83.9%) were N0 and 9 (16.1%) N+. Forty-eight (85.7%) patients underwent R0 resection and 10 (17.9%) had a complete pathological response (CPR). Thirty-day mortality rate was 5.4%, major surgical complications occurred in 6 (10.7%) patients. At the end of the follow-up, 17 (30.4%) patients were alive and 39 (69.6%) died (29 for cancer-related causes), with an overall 5-year survival of 38%. At statistical analysis, stage IIB (P = 0.003), R0 resection (P = 0.03), T3 tumour (P = 0.002) and CPR (P = 0.01) were significant independent predictors of better prognosis. CONCLUSIONS: This combined approach is feasible, and allows for a good rate of complete resection. Long-term survival rates are acceptable, especially for early stage tumours radically resected. Systemic control of disease still remains poor, with distant recurrence being the most common cause of death.

A comparative analysis of Pancoast tumour resection performed via video-assisted thoracic surgery versus standard open approaches.

OBJECTIVES: The aim of the present paper was to conduct a comparative analysis of outcomes after thoracoscopic resection versus standard thoracotomy approach in the treatment of Pancoast tumours. METHODS: All consecutive patients with Pancoast tumours undergoing surgical treatment from March 2000 to November 2012 were enrolled. Patients were divided into 2 groups according to whether a thoracoscopic or standard thoracotomy approach was adopted. In addition to morbidity and mortality, (i) intensity of pain; (ii) respiratory function focusing on the postoperative value and its variation with respect to the predicted value (Delta); (iii) analgesic consumption at different times during the postoperative course; and (iiii) survival rate were recorded in both groups and the inter-group differences were statistically compared. RESULTS: Of the 45 enrolled patients, 34 (75%) were included in the final analysis (18 in the thoracoscopic group and 16 in the standard group). Eleven (25%) patients were excluded because they (i) were unfit for surgery after induction therapy (n = 4); (ii) refused the operation (n = 1) or (iii) had unexpected pleural involvement (n = 6). Compared with the standard group, in the thoracoscopic group we observed less pain (P = 0.01), better recovery of forced vital capacity (P = 0.01) and forced expiratory value in 1 s (P < 0.001), and a reduction in opioid (P = 0.01) and analgesic consumption (P = 0.02). The median survival for all patients was 15 months. Patients with N0/N1 disease had better median survival than N2 patients (47 vs 9 months; P = 0.009). One local recurrence in the standard group was observed 1 year after operation, whereas 2 local recurrences, 1 in the thoracoscopic group and another in the standard group, were registered 2 years after the operation (P = 1.0). Finally, 4 (22%) extrathoracic metastases in the thoracoscopic group and 5 (31%) in the standard group (P = 0.8) were found over the 2 years following the procedure. CONCLUSIONS: In the management of Pancoast tumours, a thoracoscopic approach is safe and may be an effective adjunct to standard surgical resection in selected cases. Such an approach enabled surgeons to explore the pleural cavity and avoid exploratory thoracotomy in cases of unexpected pleural involvement.

Combined operative technique with anterior surgical approach and video-assisted thoracoscopic surgical lobectomy for anterior superior sulcus tumours.

Video-assisted thoracoscopic surgery (VATS) has been widely used, but surgical resections of superior sulcus tumours remain challenging because of their anatomical location. For such cases, less-invasive procedures, such as the anterior transcervical-thoracic and transmanubrial approaches, have been widely performed because of their excellent visualization of the subclavian vessels. Recently, a combined operative technique with an anterior surgical approach and VATS for anterior superior sulcus tumours has been introduced. Herein, we report three cases of anterior superior sulcus tumours successfully resected by surgical approaches combined with a VATS-based lobectomy. In all cases, operability was confirmed by VATS, and upper lobectomies with hilar and mediastinal lymph node dissections were performed. Subsequently, dissections of the anterior inlet of the tumours were performed using the transmanubrial approach in two patients and the anterior trans-cervical-thoracic approach in one patient. Both approaches provided excellent access to the anterior inlet of the tumour and exposure of the subclavian vessels, resulting in radical resection of the tumour with concomitant resection of the surrounding anatomical structures, including the chest wall and vessels. In conclusion, VATS lobectomy combined with the anterior surgical approach might be an excellent procedure for the resection of anterior superior sulcus tumours.