Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial

<p>Abstract</p> <p>Background</p> <p>Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma.</p> <p>Methods/Design</p> <p>The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A.</p> <p>Discussion</p> <p>Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00937456">NCT00937456</a> (ClinicalTrials.gov)</p

The influence of socio-economic and surveillance characteristics on breast cancer survival: a French population-based study

Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan–Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival

Implementing Grover Oracles for Quantum Key Search on AES and LowMC

Grover's search algorithm gives a quantum attack against block ciphers by searching for a key that matches a small number of plaintext-ciphertext pairs. This attack uses $O(\sqrt{N})$ calls to the cipher to search a key space of size $N$. Previous work in the specific case of AES derived the full gate cost by analyzing quantum circuits for the cipher, but focused on minimizing the number of qubits. In contrast, we study the cost of quantum key search attacks under a depth restriction and introduce techniques that reduce the oracle depth, even if it requires more qubits. As cases in point, we design quantum circuits for the block ciphers AES and LowMC. Our circuits give a lower overall attack cost in both the gate count and depth-times-width cost models. In NIST's post-quantum cryptography standardization process, security categories are defined based on the concrete cost of quantum key search against AES. We present new, lower cost estimates for each category, so our work has immediate implications for the security assessment of post-quantum cryptography. As part of this work, we release Q# implementations of the full Grover oracle for AES-128, -192, -256 and for the three LowMC instantiations used in Picnic, including unit tests and code to reproduce our quantum resource estimates. To the best of our knowledge, these are the first two such full implementations and automatic resource estimations.Comment: 36 pages, 8 figures, 14 table

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

<p>Abstract</p> <p>Background</p> <p>Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL).</p> <p>Methods</p> <p>In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.</p> <p>Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking.</p> <p>Results</p> <p>Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.</p> <p>DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations.</p> <p>Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed.</p> <p>Conclusion</p> <p>The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.</p

Quantum Collision Attacks on AES-like Hashing with Low Quantum Random Access Memories

At EUROCRYPT 2020, Hosoyamada and Sasaki proposed the first dedicated quantum attack on hash functions --- a quantum version of the rebound attack exploiting differentials whose probabilities are too low to be useful in the classical setting. This work opens up a new perspective toward the security of hash functions against quantum attacks. In particular, it tells us that the search for differentials should not stop at the classical birthday bound. Despite these interesting and promising implications, the concrete attacks described by Hosoyamada and Sasaki make use of large quantum random access memories (qRAMs), a resource whose availability in the foreseeable future is controversial even in the quantum computation community. Without large qRAMs, these attacks incur significant increases in time complexities. In this work, we reduce or even avoid the use of qRAMs by performing a quantum rebound attack based on differentials with non-full-active super S-boxes. Along the way, an MILP-based method is proposed to systematically explore the search space of useful truncated differentials with respect to rebound attacks. As a result, we obtain improved attacks on AES-MMO, AES-MP, and the first classical collision attacks on 4- and 5-round Grostl-512. Interestingly, the use of non-full-active super S-box differentials in the analysis of AES-MMO gives rise to new difficulties in collecting enough starting points. To overcome this issue, we consider attacks involving two message blocks to gain more degrees of freedom, and we successfully compress the qRAM demand of the collision attacks on AES-MMO and AES-MP (EUROCRYPT 2020) from $2^{48}$ to a range from $2^{16}$ to $0$, while still maintaining a comparable time complexity. To the best of our knowledge, these are the first dedicated quantum attacks on hash functions that slightly outperform Chailloux, Naya-Plasencia, and Schrottenloher\u27s generic quantum collision attack (ASIACRYPT 2017) in a model where large qRAMs are not available. This work demonstrates again how a clever combination of classical cryptanalytic technique and quantum computation leads to improved attacks, and shows that the direction pointed out by Hosoyamada and Sasaki deserves further investigation

Hash-based Signatures Revisited: A Dynamic FORS with Adaptive Chosen Message Security

FORS is the underlying hash-based few-time signing scheme in SPHINCS+, one of the nine signature schemes which advanced to round 2 of the NIST Post-Quantum Cryptography standardization competition. In this paper, we analyze the security of FORS with respect to adaptive chosen message attacks. We show that in such a setting, the security of FORS decreases significantly with each signed message when compared to its security against non-adaptive chosen message attacks. We propose a chaining mechanism that with slightly more computation, dynamically binds the Obtain Random Subset (ORS) generation with signing, hence, eliminating the offline advantage of adaptive chosen message adversaries. We apply our chaining mechanism to FORS and present DFORS whose security against adaptive chosen message attacks is equal to the non-adaptive security of FORS. In a nutshell, using SPHINCS+-128s parameters, FORS provides 75-bit security and DFORS achieves 150-bit security with respect to adaptive chosen message attacks after signing one message. We note that our analysis does not affect the claimed security of SPHINCS+. Nevertheless, this work provides a better understanding of FORS and other HORS variants and furnishes a solution if new adaptive cryptanalytic techniques on SPHINCS+ emerge